Antibodies and chimeric antigen receptors specific for ror1

Abstract

Provided are ROR1 binding molecules, including anti-ROR1 antibodies, including antibody fragments such as variable heavy chain (VH) regions, single-chain fragments, and chimeric receptors including the antibodies, such as chimeric antigen receptors (CARs). In some embodiments, the antibodies specifically bind to ROR1. Among the antibodies are human antibodies, including those that compete for binding to ROR1 with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the chimeric receptors, and uses of the binding molecules and cells adoptive cell therapy.

1 . An antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment comprising a heavy chain variable (V H ) region comprising:
 a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence set forth in SEQ ID NO: 22, 29, 35, 45, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 or 174; or   a CDR-H3 contained within the heavy chain variable (V H ) sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209.   
     
     
         2 . An antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment comprising a heavy chain variable (V H ) region comprising at least 90% sequence identity to the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209. 
     
     
         3 . The antibody or antigen-binding fragment thereof of  claim 2 , said antibody or antigen-binding fragment comprising a heavy chain variable (V H ) region comprising at least 90% sequence identity to the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19. 
     
     
         4 . The antibody or fragment of  claim 2  or  claim 3 , wherein the V H  region comprises a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence set forth in SEQ ID NO: 92, 93, 94, 109 or 110. 
     
     
         5 . The antibody or fragment of any of  claims 2 - 4 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence set forth in SEQ ID NO: 22, 29, 35, 45, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 or 174; or   a CDR-H3 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209.   
     
     
         6 . The antibody or fragment of any of  claims 2 - 5 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence set forth in SEQ ID NO: 22, 29, 35, 45, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 or 71; or   a CDR-H3 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19.   
     
     
         7 . The antibody or fragment of any of  claims 2 - 6 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence set forth in SEQ ID NO: 22, 29, 35 or 52; or   a CDR-H3 contained within the V H  sequence set forth in SEQ ID NO: 10, 13, 15 or 19.   
     
     
         8 . The antibody or fragment of  claim 2  or  claim 3 , wherein the V H  region comprises a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 72 or a CDR-H3 contained within the V H  sequence set forth in SEQ ID NO: 85. 
     
     
         9 . The antibody or fragment of any of  claims 1 - 8 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence set forth in SEQ ID NO:95 or 97; and/or   a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence set forth in SEQ ID NO: 96 or 98.   
     
     
         10 . The antibody or fragment of any of  claims 1 - 9 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence set forth in SEQ ID NO: 20, 27, 33, 155, 156, 157, 158, 159, 160, 161, 162 or 163 and/or comprising the amino acid sequence set forth in SEQ ID NO: 269, 270, 271, 272, 273, 274, 275, 276, 278 or 279 and/or comprising the amino acid sequence set forth in SEQ ID NO: 75, 77, 79, 280, 281, 282, 283, 284, 285, 286, 287, 288 or 289 and/or a CDR-H1 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209; and/or   a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence set forth in SEQ ID NO: 21, 26, 28, 34, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173 or 318, and/or comprising the amino acid sequence set forth in SEQ ID NO: 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302 or 303 and/or comprising the amino acid sequence set forth in SEQ ID NO: 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316 or 317 and/or a CDR-H2 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209.   
     
     
         11 . The antibody or fragment of any of  claims 1 - 10 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence set forth in SEQ ID NO: 20, 27, or 33 and/or a CDR-H1 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19; and/or   a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence set forth in SEQ ID NO: 21, 26, 28, or 34 and/or a CDR-H2 contained within the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19.   
     
     
         12 . The antibody or fragment of any of  claims 1 - 11 , wherein the V H  region comprises:
 a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence set forth in SEQ ID NO: 20, 27, or 33 and/or a CDR-H1 contained within the V H  sequence set forth in SEQ ID NO: 10, 13, 15 or 19; and/or   a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence set forth in SEQ ID NO: 26, 28, or 34 and/or a CDR-H2 contained within the V H  sequence set forth in SEQ ID NO: 10, 13, 15 or 19.   
     
     
         13 . An antibody or antigen-binding fragment thereof, comprising a heavy chain variable (V H ) region comprising a heavy chain complementarity determining region 1 (CDR-H1), CDR-H2, and CDR-H3, wherein:
 the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 20, 27, 33, 75, 77, 79, 155, 156, 157, 158, 159, 160, 161, 162, 163, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278 or 279;   the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 21, 26. 28. 34, 80, 81, 82, 83, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303 or 318; and/or   the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 22, 29, 35, 45, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 or 174.   
     
     
         14 . The antibody or antigen-binding fragment of  claim 11 , wherein:
 the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 20, 27, or 33;   the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 21, 26, 28, or 34; and/or   the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 22, 29, 35, 45, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 or 71.   
     
     
         15 . The antibody or fragment of any of  claims 1 ,  4 - 7  and  9 - 14 , wherein the CDR-H3 comprises the amino acid sequence VSNYEYYFDY (SEQ ID NO: 29), DFGRWGYYFDY (SEQ ID NO: 52), DFGRWSYYFDY (SEQ ID NO:35) or DSSYDAFDI (SEQ ID NO:22). 
     
     
         16 . The antibody or fragment of any of  claims 1 - 7  and  9 - 15 , comprising a heavy chain variable (V H ) region comprising a heavy chain complementarity determining region 1 (CDR-H1), CDR-H2, and CDR-H3, wherein:
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 20, 21, and 22, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 20, 26, and 22, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 28, and 29, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34, and 35, respectively; or 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34, and 52, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 164 and 45, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 164 and 68, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 164 and 64, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 164 and 66, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 having the sequences of SEQ ID NOs: 33, 318, and 35, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 70, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 55, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 53, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 56, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 61, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34 and 59, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 171 and 60, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 155, 34 and 35, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 156, 34 and 35, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 162, 170 and 50, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 162, 170 and 51, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 161, 169 and 54, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs:159, 167 and 57, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 160, 168 and 58, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 158, 166 and 62, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 158, 166 and 63, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 158, 166 and 65, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 157, 165 and 67, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 163, 173 and 69, respectively; or 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 160, 172, 71, respectively; or 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 160, 172, 174, respectively. 
 
     
     
         17 . The antibody or fragment of any of  claims 1 - 7  and  9 - 16 , comprising a heavy chain variable (V H ) region comprising a heavy chain complementarity determining region 1 (CDR-H1), CDR-H2, and CDR-H3, wherein:
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 20, 21, and 22, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 20, 26, and 22, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 27, 28, and 29, respectively; 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34, and 35, respectively; or 
 the CDR-H1, CDR-H2, and CDR-H3 comprise the sequences of SEQ ID NOs: 33, 34, and 52, respectively. 
 
     
     
         18 . An antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region comprising a heavy chain complementarity determining region 1 (CDR-H1), a CDR-H2, and a CDR-H3, respectively, comprising the amino acid sequences of a CDR-H1, a CDR-H2, and a CDR-H3 contained within the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209. 
     
     
         19 . The antibody or antigen-binding fragment of  claim 18 , wherein the CDR-H1, CDR-H2, and CDR-H3, respectively, comprise the amino acid sequences of a CDR-H1, a CDR-H2, and a CDR-H3 contained within the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19. 
     
     
         20 . The antibody or fragment of any of  claims 1 - 19 , wherein the V H  region comprises a framework region 1 (FR1), a FR2, a FR3, and/or a FR4 comprising at least 90% sequence identity, respectively, to a FR1, FR2, FR3, and/or FR4 of the amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209. 
     
     
         21 . The antibody or fragment of any of  claims 1 - 20 , wherein the V H  region comprises a framework region 1 (FR1), a FR2, a FR3, and/or a FR4 comprising at least 90% sequence identity, respectively, to a FR1, FR2, FR3, and/or FR4 of the amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17 or 19. 
     
     
         22 . The antibody or fragment of any of  claims 1 - 7  and  9 - 21 , wherein the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209. 
     
     
         23 . The antibody or fragment of any of  claims 1 - 7  and  9 - 22 , wherein the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19. 
     
     
         24 . The antibody or fragment of  claim 23 , wherein the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 8 or 10. 
     
     
         25 . The antibody or fragment of any of  claims 1 - 7  and  9 - 24 , wherein the V H  region comprises the CDR-H1, CDR-H2, and CDR-H3 set forth in SEQ ID NOS: 20, 26, and 22, respectively, or set forth in SEQ ID NOS: 269, 294 or 22, respectively, and/or the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 19. 
     
     
         26 . The antibody or fragment of any of  claims 1 - 7  and  9 - 24 , wherein the V H  region comprises the CDR-H1, CDR-H2, and CDR-H3 set forth in SEQ ID NOS: 33, 34, and 52, respectively, or set forth in SEQ ID NOS: 271, 291 and 52, respectively, and/or the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 10. 
     
     
         27 . The antibody or fragment of any of  claims 1 - 7  and  9 - 24 , wherein the V H  region comprises the CDR-H1, CDR-H2, and CDR-H3 set forth in SEQ ID NOS: 33, 34, and 35, respectively, or set forth in SEQ ID NOS: 271, 291 and 35, respectively, and/or the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 13. 
     
     
         28 . The antibody or fragment of any of  claims 1 - 7  and  9 - 24 , wherein the V H  region comprises the CDR-H1, CDR-H2, and CDR-H3 set forth in SEQ ID NOS: 27, 28, and 29, respectively, or set forth in SEQ ID NOS: 279, 292 and 29, respectively, and/or the V H  region comprises the sequence of amino acids set forth in SEQ ID NO: 15. 
     
     
         29 . The antibody or fragment of any of  claims 1 - 28 , wherein the antibody or fragment does not comprise a light chain variable (VL) region, does not comprise a CDR-L1, CDR-L2, and/or CDR-L3, and/or is a single-domain antibody (sdAb) comprising only the V H  region. 
     
     
         30 . The antibody or fragment of any of  claims 1 - 29  that is a sdAb comprising only the V H  region. 
     
     
         31 . The antibody or fragment of any of  claims 1 - 28 , wherein the antibody or fragment further comprises a light chain variable (VL) region. 
     
     
         32 . The antibody or fragment of  claim 31 , wherein the V L  region comprises at least 90% sequence identity to the V L  region amino acid sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248. 
     
     
         33 . The antibody or fragment of  claim 31  or  claim 32 , wherein the V L  region comprises at least 90% sequence identity to the V L  region amino acid sequence set forth in SEQ ID NO: 14, 16, or 18. 
     
     
         34 . The antibody of fragment of any of  claims 31 - 33 , wherein the V L  region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence set forth in SEQ ID NO: 99 or 100. 
     
     
         35 . The antibody or fragment of any of  claims 31 - 34 , wherein the V L  region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence set forth in SEQ ID NO: 25, 32, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 232 or 233. 
     
     
         36 . The antibody or fragment of any of  claims 31 - 35 , wherein the V L  region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence set forth in SEQ ID NO: 25, 32, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48 or 49. 
     
     
         37 . The antibody or fragment of any of  claims 31 - 36 , wherein the V L  region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence set forth in SEQ ID NO: 101 and/or a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence set forth in SEQ ID NO: 102. 
     
     
         38 . The antibody or fragment of any of  claims 31 - 38 , wherein the V L  region comprises:
 a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence set forth in SEQ ID NO: 23, 30, 36, 210, 211, 212, 213, 214, 215, 217, 216, 218, 219 or 220 and/or a CDR-L1 contained within the V L  sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248; and/or   a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence set forth in SEQ ID NO: 24, 31, 37, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230 or 231 and/or a CDR-L2 contained within the V L  sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248.   
     
     
         39 . The antibody or fragment of any of  claims 31 - 38 , wherein the V L  region comprises:
 a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence set forth in SEQ ID NO: 23, 30, or 36 and/or a CDR-L1 contained within the V L  sequence set forth in SEQ ID NO: 14, 16, or 18; and/or   a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence set forth in SEQ ID NO: 24, 31, or 37 and/or a CDR-L2 contained within the V L  sequence set forth in SEQ ID NO: 14, 16, or 18.   
     
     
         40 . The antibody or fragment of any of  claims 31 - 39 , wherein the V L  region comprises:
 a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence set forth in SEQ ID NO: 23, 30, 36, 210, 211, 212, 213, 214, 215, 217, 216, 218, 219 or 220;   a light chain complementarity determining region 2 (CDR-L2), comprising the amino acid sequence set forth in SEQ ID NO: 24, 31, 37, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230 or 231; and   a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence set forth in SEQ ID NO: 25, 32, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 232 or 233.   
     
     
         41 . The antibody or fragment of any of  claims 31 - 40 , wherein the V L  region comprises:
 a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence set forth in SEQ ID NO: 23, 30, or 36;   a light chain complementarity determining region 2 (CDR-L2), comprising the amino acid sequence set forth in SEQ ID NO: 24, 31, or 37; and   a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence set forth in SEQ ID NO: 25, 32, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, or 49.   
     
     
         42 . The antibody or fragment of any of  claims 36 - 41 , wherein the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 25, 32 or 38. 
     
     
         43 . The antibody or fragment of any of  claims 31 - 42 , wherein the V L  region comprises a CDR-L1, CDR-L2, and CDR-L3 selected from:
 the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 23, 24, and 25, respectively;   the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 30, 31, and 32, respectively;   the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 36, 37, and 38, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 216, 227, and 40, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 218, 229, and 39, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 219, 230, and 43, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 220, 231, and 46, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 210, 221, and 49, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 210, 221, and 233, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 211, 222, and 48, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 212, 223, and 42, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 214, 225, and 232, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 215, 226, and 44, respectively;   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 217, 228, and 41, respectively; or   the CDR-L1, CDR-L2 and CDR-L3 comprising the sequences of SEQ ID NOs: 213, 224, and 47, respectively.   
     
     
         44 . The antibody or fragment of any of  claims 31 - 43 , wherein the V L  region comprises a CDR-L1, CDR-L2, and CDR-L3 selected from:
 the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 23, 24, and 25, respectively;   the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 30, 31, and 32, respectively; or   the CDR-L1, CDR-L2, and CDR-L3 comprising the sequences of SEQ ID NOs: 36, 37, and 38, respectively.   
     
     
         45 . The antibody or fragment of any of  claims 31 - 44 , wherein the V L  region comprises light chain complementarity determining region 1 (CDR-L1), CDR-L2, and CDR-L3, respectively, contained within the V L  region amino acid sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248. 
     
     
         46 . The antibody or fragment of any of  claims 31 - 45 , wherein the V L  region comprises light chain complementarity determining region 1 (CDR-L1), CDR-L2, and CDR-L3, respectively, contained within the V L  region amino acid sequence set forth in SEQ ID NO: 14, 16, or 18. 
     
     
         47 . The antibody or fragment of any of  claims 31 - 46 , wherein the V L  region comprises a framework region 1 (FR1), a FR2, a FR3, and/or a FR4 comprising at least 90% sequence identity, respectively, to the FR1, FR2, FR3, and/or FR4 of the amino acid sequence set forth in SEQ ID NO: 14, 16, or 18. 
     
     
         48 . The antibody or fragment of any of  claims 31 - 47 , wherein the V L  region comprises the amino acid sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248. 
     
     
         49 . The antibody or fragment of any of  claims 31 - 48 , wherein the V L  region comprises the amino acid sequence set forth in SEQ ID NO: 14, 16, or 18. 
     
     
         50 . An antibody or antigen-binding fragment thereof, comprising:
 a heavy chain complementarity determining regions 1, 2, and 3 (CDR-H1, CDR-H2, and CDR-H3), respectively comprising the amino acid sequences of CDR-H1, CDR-H2, and CDR-H3 sequences contained within the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209; and/or   a light chain complementarity determining regions 1, 2, and 3 (CDR-L1, CDR-L2, and CDR-L3), respectively comprising the amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 sequences contained within the light chain variable (VL) region amino acid sequence set forth in SEQ ID NO: 14, 16, 18, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 or 248.   
     
     
         51 . The antibody or antigen-binding fragment of  claim 50 , wherein:
 the CDR-H1, CDR-H2, and CDR-H3, respectively, comprise the amino acid sequences of CDR-H1, CDR-H2, and CDR-H3 sequences contained within the V H  region amino acid sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19; and/or   the CDR-L1, CDR-L2, and CDR-L3, respectively, comprise the amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 sequences contained within the light chain variable (VL) region amino acid sequence set forth in SEQ ID NO: 14, 16, or 18.   
     
     
         52 . An antibody or antigen-binding fragment thereof, comprising:
 a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 19 and 18, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 17 and 18, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 15 and 16, respectively; or   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 13 and 14, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 182 and 242 respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 182 and 246, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 182 and 247, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 185 and 248, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 186 and 248, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 175 and 234, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 175 and 235, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 176 and 236, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 176 and 237, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 177 and 238, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 179 and 240 respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 180 and 241, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 181 and 241, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 183 and 243 respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 183 and 244 respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 184 and 243, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 184 and 244 respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 183 and 245, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 184 and 245, respectively; or   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 178 and 239, respectively.   
     
     
         53 . The antibody or antigen-binding fragment of  claim 52 , comprising:
 a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 19 and 18, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 17 and 18, respectively;   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 15 and 16, respectively; or   a V H  and V L  regions comprising amino acid sequences having at least 90% identity to SEQ ID NOs: 13 and 14, respectively.   
     
     
         54 . The antibody or fragment of  claim 52  or  claim 53 , wherein:
 the V H  and V L  regions comprise the amino acid sequences of SEQ ID NOs: 19 and 18, respectively; 
 the V H  and V L  regions comprise the amino acid sequences of SEQ ID NOs: 17 and 18, respectively; 
 the V H  and V L  regions comprise the amino acid sequences of SEQ ID NOs: 15 and 16 respectively; or 
 the V H  and V L  regions comprise the amino acid sequences of SEQ ID NOs: 13 and 14 respectively. 
 
     
     
         55 . The antibody or fragment of any of  claims 1 - 54 , wherein said antibody or fragment specifically binds to a ROR1 protein. 
     
     
         56 . The antibody or fragment of  claim 55 , wherein the ROR1 protein is a human ROR1 protein. 
     
     
         57 . The antibody or fragment of  claim 55 , wherein the ROR1 protein is a mouse ROR1 protein. 
     
     
         58 . The antibody or fragment of any of  claims 1 - 57 , wherein:
 said antibody or fragment has a binding affinity for a ROR1 protein with an EC50 that is from or from about 0.1 nM to 100 nM, 0.5 nM to 50 nM or 1 nM to 10 nM; or   said antibody or fragment has a binding affinity for a ROR1 protein with an EC50 that is less than or less than about 100 nM, less than or less than about 50 nM, less than or less than about 10 nM or less than or less than about 1 nM.   
     
     
         59 . The antibody or fragment of any of  claims 1 - 58 , wherein said antibody or fragment has a binding affinity for a human ROR1 protein that is at least as high or substantially as high as the binding affinity for the ROR1 protein of the corresponding form of the anti-ROR1 antibody R12 or antigen-binding fragment thereof, which is optionally an scFv fragment of R12. 
     
     
         60 . The antibody or fragment of any of  claims 1 - 59 , wherein said antibody or fragment specifically binds to the same or an overlapping epitope of a human ROR1 protein as the epitope specifically bound by the anti-ROR1 antibody R12 or an antigen-binding fragment thereof, which is optionally an scFv fragment of R12. 
     
     
         61 . The antibody or fragment of any of  claims 1 - 60 , wherein said antibody or fragment competes for binding to a human ROR1 protein with anti-ROR1 antibody R12 or an antigen-binding fragment thereof, which is optionally an scFv fragment of R12. 
     
     
         62 . The antibody or fragment of any of  claims 1 - 61 , wherein said antibody or fragment inhibits the binding of the anti-ROR1 antibody R12 or an antigen-binding fragment thereof, which is optionally an scFv fragment of R12, to a human ROR1 protein by greater than or greater than about 80% or greater than or greater than about 90%. 
     
     
         63 . The antibody or fragment of any of  claims 1 - 62 , wherein the antibody or fragment binds to an overlapping epitope of a human ROR1 protein as the epitope specifically bound by the anti-ROR1 antibody R12 or an antigen-binding fragment thereof, which is optionally an scFv fragment of R12 and the antibody or fragment binds to mouse ROR1. 
     
     
         64 . The antibody or antigen-binding fragment of any of  claims 55 ,  56  and  58 - 63 , wherein said human ROR1 protein comprises an amino acid sequence set forth in SEQ ID NO: 103. 
     
     
         65 . The antibody or antigen-binding fragment of any of  claims 55 ,  56  and  58 - 64 , which
 binds an epitope within an extracellular portion of the ROR1 protein; and/or 
 binds to an epitope of said ROR1 protein comprising residues within the fz domain or the Ig domain of the ROR1 protein. 
 
     
     
         66 . The antibody or antigen-binding fragment of  claim 65 , wherein the epitope comprises a residue within the fz domain of the ROR1 protein and a residue within the Ig domain of the ROR1 protein. 
     
     
         67 . The antibody or antigen-binding fragment thereof of  claim 65  or  claim 66 , wherein said Ig domain comprises residues 13-118 of the amino acid sequence set forth in SEQ ID NO: 103; and/or said fz domain comprises residues 136-270 of the amino acid sequence set forth in SEQ ID NO:103. 
     
     
         68 . The antibody or antigen binding fragment of  claim 65 , wherein the extracellular portion comprises amino acids 1-377 of SEQ ID NO:103. 
     
     
         69 . The antibody or fragment thereof of any of  claims 1 - 56 ,  58 - 62  and  64 - 68 , wherein the antibody does not specifically bind to a mouse ROR1 protein or does not specifically bind to a protein having the amino acid sequence set forth in SEQ ID NO: 106. 
     
     
         70 . The antibody or fragment of any of  claims 1 - 7  and  9 - 69 , which does not comprise the CDR-H1, CDR-H2, CDR-H3 and/or CDR-L1, CDR-L2, CDR-L3 sequences of the anti-ROR1 antibody, R12, and/or of the anti-ROR1 antibody 2A2. 
     
     
         71 . The antibody or fragment of any of  claims 1 - 7  and  9 - 70 , which does not comprise CDR-H1, CDR-H2, CDR-H3 and/or CDR-L1, CDR-L2, CDR-L3 sequences having at least 90% identity to the CDR-H1, CDR-H2, CDR-H3 and/or CDR-L1, CDR-L2, CDR-L3 sequences of the anti-ROR1 antibody, R12, and/or of the anti-ROR1 antibody 2A2. 
     
     
         72 . The antibody or fragment of any of  claims 1 - 71 , wherein the antibody or fragment is human. 
     
     
         73 . A human antibody or antigen-binding fragment thereof that specifically binds to the same or an overlapping epitope of a ROR1 protein as the epitope specifically bound by a reference antibody, wherein the reference antibody is the antibody or fragment thereof of any of  claims 1 - 72  or is the anti-ROR1 antibody, R12, or antigen binding fragment thereof, said human antibody or fragment comprising heavy and light chain CDRs that are distinct from the CDRs present in R12 and/or 2A2. 
     
     
         74 . A human antibody or antigen-binding fragment thereof that specifically binds to ROR1 and competes for binding to ROR1 with a reference antibody, wherein the reference antibody is the antibody or fragment of any of  claims 1 - 72  or is the anti-ROR1 antibody R12 or an antigen binding fragment thereof, said human antibody or fragment comprising heavy and light chain CDRs that are distinct from the CDRs present in R12 and/or 2A2. 
     
     
         75 . The human antibody or fragment of any of  claims 72 - 74 , wherein:
 the antibody comprises a heavy chain variable (V H ) region, said V H  region comprises a portion having at least 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by a germline nucleotide human heavy chain V segment, a portion with at least 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by a germline nucleotide human heavy chain D segment, and/or a portion having at least 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by a germline nucleotide human heavy chain J segment; and/or   the antibody comprises a light chain variable (V L ) region, said V L  region comprises a portion with at least 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by a germline nucleotide human kappa or lambda chain V segment, and/or a portion with at least 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by a germline nucleotide human kappa or lambda chain J segment.   
     
     
         76 . The human antibody or fragment of any of  claims 72 - 75 , wherein:
 the CDR-H1 and/or CDR-H2 comprises a sequence 100% identical or with no more than one amino acid difference as compared to an amino acid sequence of a CDR-H1 and/or CDR-H2, respectively, within a sequence encoded by a germline nucleotide human heavy chain V segment; and/or   the CDR-L1 and/or CDR-L2 comprises a sequence 100% identical or with no more than one amino acid difference as compared to an amino acid sequence of a CDR-L1 and/or CDR-L2, respectively, within a sequence encoded by a germline nucleotide human kappa or lambda v segment.   
     
     
         77 . The antibody or fragment of any of  claims 1 - 76 , wherein the antibody or fragment is recombinant. 
     
     
         78 . The antibody or fragment of any of  claims 1 - 77 , which is monoclonal. 
     
     
         79 . The antibody or fragment of any of  claims 1 - 78  that is an antigen-binding fragment. 
     
     
         80 . The antibody or fragment of any of any of  claims 1 - 79 , which is a single chain fragment. 
     
     
         81 . The antibody or fragment of any of  claims 31 - 80 , which is a fragment comprising antibody V H  and V L  regions joined by a flexible linker. 
     
     
         82 . The antibody or fragment of  claim 80  or  claim 81 , wherein the fragment comprises an scFv. 
     
     
         83 . The antibody or fragment of  claim 82 , wherein the scFv comprises a linker comprising the sequence set forth SEQ ID NO: 91. 
     
     
         84 . The antibody or fragment of  claim 82  or  claim 83 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, 12, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267 or 268, or a sequence of amino acids that exhibits at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, 12, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267 or 268. 
     
     
         85 . The antibody or fragment of any of  claims 82 - 84 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, or 12, or a sequence of amino acids that exhibits at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, or 12. 
     
     
         86 . The antibody or fragment of any of  claims 82 - 85 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, or 12. 
     
     
         87 . The antibody or fragment of any of  claims 31 - 86 , wherein the antibody or fragment comprises the V H  region set forth in SEQ ID NO: 19 and the V L  region set forth in SEQ ID NO: 18, and/or the antibody or fragment comprises the sequence of amino acids set forth in SEQ ID NO: 12. 
     
     
         88 . The antibody or fragment of any of  claims 31 - 86 , wherein the antibody or fragment comprises the V H  region set forth in SEQ ID NO: 13 and the V L  region set forth in SEQ ID NO: 14, and/or the antibody or fragment comprises the sequence of amino acids set forth in SEQ ID NO: 6. 
     
     
         89 . The antibody or fragment of any of  claims 31 - 86 , wherein the antibody or fragment comprises the V H  region set forth in SEQ ID NO: 15 and the V L  region set forth in SEQ ID NO: 16, and/or the antibody or fragment comprises the sequence of amino acids set forth in SEQ ID NO: 4. 
     
     
         90 . The antibody or fragment of any of  claims 31 - 86 , wherein the antibody or fragment comprises the V H  region set forth in SEQ ID NO: 17 and the V L  region set forth in SEQ ID NO: 18, and/or the antibody or fragment comprises the sequence of amino acids set forth in SEQ ID NO: 2. 
     
     
         91 . A single chain cell-surface protein, comprising the antibody or fragment of any of  claims 1 - 90 . 
     
     
         92 . A single chain cell surface protein comprising the scFv sequence of SEQ ID NO: 2, 4, 6, 12, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267 or 268 or comprising the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, 19, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 or 209. 
     
     
         93 . The single chain cell surface protein of  claim 92 , comprising the scFv sequence of SEQ ID NO: 2, 4, 6 or 12 or comprising the V H  sequence set forth in SEQ ID NO: 8, 10, 13, 15, 17, or 19. 
     
     
         94 . The antibody or fragment of any of  claims 1 - 90 , which further comprises at least a portion of an immunoglobulin constant region. 
     
     
         95 . The antibody or fragment of  claim 94 , further comprising a spacer set forth in SEQ ID NO:108. 
     
     
         96 . The antibody or fragment of  claim 94 , wherein the at least a portion of an immunoglobulin constant region comprises an Fc region. 
     
     
         97 . The antibody or fragment of  claim 96 , wherein the Fc region is an Fc region of a human IgG. 
     
     
         98 . A conjugate, comprising the antibody or fragment of any of  claims 1 - 97  and a heterologous molecule or moiety. 
     
     
         99 . A chimeric antigen receptor (CAR) comprising an extracellular portion comprising the antibody or fragment of any of  claims 1 - 97  and an intracellular signaling domain. 
     
     
         100 . The chimeric antigen receptor of  claim 99 , wherein the antibody or fragment comprises a VH sdAb, an scFv and the intracellular signaling domain comprises an ITAM. 
     
     
         101 . The chimeric antigen receptor of  claim 99  or  100 , wherein the intracellular signaling domain comprises a signaling domain of a zeta chain of a CD3-zeta (CD3) chain. 
     
     
         102 . The chimeric antigen receptor of any of  claims 99 - 101 , further comprising a transmembrane domain linking the extracellular domain and the intracellular signaling domain. 
     
     
         103 . The chimeric antigen receptor of  claim 102 , wherein the transmembrane domain comprises a transmembrane portion of CD28. 
     
     
         104 . The chimeric antigen receptor of any of  claims 99 - 103 , further comprising an intracellular signaling domain of a T cell costimulatory molecule. 
     
     
         105 . The chimeric antigen receptor of  claim 104 , wherein the T cell costimulatory molecule is selected from the group consisting of CD28 and 41BB. 
     
     
         106 . A nucleic acid encoding the antibody or fragment thereof of any of  claims 1 - 97 , conjugate of  claim 98  or the chimeric antigen receptor of any of  claims 99 - 105 . 
     
     
         107 . An engineered cell expressing a receptor comprising the antibody or fragment of any of  claims 1 - 97 , conjugate of  claim 98  or the chimeric antigen receptor of any of  claims 99 - 105 . 
     
     
         108 . The engineered cell of  claim 107 , which is a T cell. 
     
     
         109 . A composition comprising the antibody or fragment thereof of any of  claims 1 - 97 , conjugate of  claim 98 , the CAR of any of  claims 99 - 105 , or the cell of  claim 107  or  108 . 
     
     
         110 . The composition of  claim 109 , further comprising a pharmaceutically acceptable excipient. 
     
     
         111 . A method of treatment, comprising administering the composition of  claim 109  or  claim 110  to a subject having a disease or disorder associated with ROR1. 
     
     
         112 . A method of treatment, comprising administering an antibody or fragment of any of  claims 1 - 97 , conjugate of  claim 98 , a CAR of any of  claims 99 - 103  or the cell of  claim 107  or  108  to a subject having a disease or disorder associated with ROR1. 
     
     
         113 . A method of treatment, comprising administering the cell of  claim 107  or  claim 108  to a subject having a disease or disorder associated with ROR1. 
     
     
         114 . The method of any of  claims 112 - 113 , wherein the disease or disorder is a ROR1-expressing cancer. 
     
     
         115 . The method of claim any of  claims 112 - 114 , wherein the ROR1-expressing cancer is selected from the group consisting of B cell leukemia, lymphoma, B cell chronic lymphocytic leukemia (CLL), AML, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), Burkett's Lymphoma, mantle cell lymphoma (MCL), non-small cell lung cancer (NSCLC), neuroblastoma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell cancer, melanoma, myeloma, stomach cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, uterine cancer, adrenal cancer and head and neck cancer. 
     
     
         116 . A composition of  claim 109  or  claim 110  for use in treating a disease or disorder associated with ROR1. 
     
     
         117 . Use of a composition of  claim 109  or  claim 110  for the manufacture of a medicament for treating a disease or disorder associated with ROR1. 
     
     
         118 . The composition for use of  claim 116  or the use of  claim 117 , wherein the disease or disorder is a ROR1-expressing cancer. 
     
     
         119 . The composition for use or use of  claim 118 , wherein the ROR1-expressing cancer is selected from the group consisting of B cell leukemia, lymphoma, B cell chronic lymphocytic leukemia (CLL), AML, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), Burkett's Lymphoma, mantle cell lymphoma (MCL), non-small cell lung cancer (NSCLC), neuroblastoma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell cancer, melanoma, myeloma, stomach cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, uterine cancer, adrenal cancer and head and neck cancer.