Anti-cd33 antibodies and methods of use thereof

Abstract

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind one or more epitopes within a CD33 protein, e.g., human CD33 or a mammalian CD33, and have improved and/or enhanced functional characteristics, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

What is claimed is: 
     
         1 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
 an HVR-H1 comprising a sequence according to Formula I: GX 1 X 2 X 3 TDYNX 4 H (SEQ ID NO: 152), wherein X 1  is Y, A, or V, X 2  is T or A, X 3  is F, E, or H, and X 4  is L, F, Y, or N;   an HVR-H2 comprising a sequence according to Formula II: FIYPX 1 NX 2 IX 3 G (SEQ ID NO: 153), wherein X 1  is S or A, X 2  is G, Q, R, or V, and X 3  is T or R; and   an HVR-H3 comprising a sequence according to Formula III: SX 1 VDYFDX 2  (SEQ ID NO: 154), wherein X 1  is T, D, F, or S, and X 2  is Y, D, or L; and   
       wherein the antibody is not an antibody comprising a heavy chain variable region comprising an HVR-H1 comprising the sequence of GYTFTDYNLH (SEQ ID NO: 105), an HVR-H2 comprising the sequence of FIYPSNGITG (SEQ ID NO: 115), and an HVR-H3 comprising the sequence of STVDYFDY (SEQ ID NO: 121). 
     
     
         2 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the light chain variable region comprises:
 an HVR-L1 comprising a sequence according to Formula IV: X 1 X 2 SQX 3 VX 4 X 5 STYSYMH (SEQ ID NO: 155), wherein X 1  is R or K, X 2  is A, G, or V, X 3  is S or D, X 4  is S, G, or H, and X 5  is T or A;   an HVR-L2 comprising a sequence according to Formula V: YX 1 X 2 X 3 X 4 X 5 S (SEQ ID NO: 156), wherein X 1  is A, V, or E, X 2  is 5, V, or F, X 3  is N, A, Y, or F, X 4  is L or V, and X 5  is E, G, or N; and   an HVR-L3 comprising a sequence according to Formula VI: X 1 HSX 2 X 3 X 4 PLX 5  (SEQ ID NO: 157), wherein X 1  is Q or E, X 2  is W or E, X 3  is E or A, X 4  is I or L, and X 5  is T or E; and   wherein the antibody is not an antibody comprising a light chain variable region comprising an HVR-L1 comprising the sequence of RASQSVSTSTYSYMH (SEQ ID NO: 127), an HVR-L2 comprising the sequence of YASNLES (SEQ ID NO: 135), and an HVR-L3 comprising the sequence of QHSWEIPLT (SEQ ID NO: 146).   
     
     
         3 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
 an HVR-H1 comprising a sequence according to Formula I: GX 1 X 2 X 3 TDYNX 4 H (SEQ ID NO: 152), wherein X 1  is Y, A, or V, X 2  is T or A, X 3  is F, E, or H, and X 4  is L, F, Y, or N;   an HVR-H2 comprising a sequence according to Formula II: FIYPX 1 NX 2 IX 3 G (SEQ ID NO: 153), wherein X 1  is S or A, X 2  is G, Q, R, or V, and X 3  is T or R; and   an HVR-H3 comprising a sequence according to Formula III: SX 1 VDYFDX 2  (SEQ ID NO: 154), wherein X 1  is T, D, F, or S, and X 2  is Y, D, or L; and   
       the light chain variable region comprises:
 an HVR-L1 comprising a sequence according to Formula IV: X 1 X 2 SQX 3 VX 4 X 5 STYSYMH (SEQ ID NO: 155), wherein X 1  is R or K, X 2  is A, G, or V, X 3  is S or D, X 4  is S, G, or H, and X 5  is T or A; 
 an HVR-L2 comprising a sequence according to Formula V: YX 1 X 2 X 3 X 4 X 5 S (SEQ ID NO: 156), wherein X 1  is A, V, or E, X 2  is 5, V, or F, X 3  is N, A, Y, or F, X 4  is L or V, and X 5  is E, G, or N; and 
 an HVR-L3 comprising a sequence according to Formula VI: X 1 HSX 2 X 3 X 4 PLX 5  (SEQ ID NO: 157), wherein X 1  is Q or E, X 2  is W or E, X 3  is E or A, X 4  is I or L, and X 5  is T or E; and 
 
       wherein the antibody is not an antibody comprising a heavy chain variable region comprising an HVR-H1 comprising the sequence of GYTFTDYNLH (SEQ ID NO: 105), an HVR-H2 comprising the sequence of FIYPSNGITG (SEQ ID NO: 115), and an HVR-H3 comprising the sequence of STVDYFDY (SEQ ID NO: 121), and a light chain variable region comprising an HVR-L1 comprising the sequence of RASQSVSTSTYSYMH (SEQ ID NO: 127), an HVR-L2 comprising the sequence of YASNLES (SEQ ID NO: 135), and an HVR-L3 comprising the sequence of QHSWEIPLT (SEQ ID NO: 146). 
     
     
         4 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the HVR-H1, HVR-H2, and HVR-H3 of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Tables 9A to 9C). 
     
     
         5 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the light chain variable region comprises the HVR-L1, HVR-L2, and HVR-L3 of antibody AB-14.3, AB-14.4, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, or AB-64.8 (as shown in Tables 10A to 10C). 
     
     
         6 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the HVR-H1, HVR-H2, and HVR-H3 of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Tables 9A to 9C); and the light chain variable region comprises the HVR-L1, HVR-L2, and HVR-L3 of antibody AB-14.3, AB-14.4, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, or AB-64.8 (as shown in Tables 10A to 10C). 
     
     
         7 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region comprising an HVR-H1, HVR-H2, and HVR-H3 and a light chain variable region comprising an HVR-L1, HVR-L2, and HVR-L3, wherein the antibody comprises the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Tables 9A to 9C and 10A to 10C). 
     
     
         8 . The antibody of any one of  claims 1 - 7 , wherein the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein:
 VH FR1 comprises a sequence according to Formula VII:   QVQLVQSGAEVKKPGX 1 SVKX 2 SCKAS (SEQ ID NO: 158), wherein X 1  is A or S, and X 2  is V or I;   VH FR2 comprises the sequence of SEQ ID NO: 5;   VH FR3 comprises a sequence according to Formula VIII:   X 1 AX 2 X 3 X 4 X 5 X 6 RX 7 TX 8 TVDX 9 X 10 X 11 STX 12 YMELSSLRSEDTAVYYCAR (SEQ ID NO: 159), wherein X 1  is Y or S, X 2  is Q or E, X 3  is K or D, X 4  is F or D, X 5  is Q, F, E, or T, X 6  is G, D, or H, X 7  is V or A, X 8  is M or L, X 9  is T, N, or Q, X 10  is S or P, X 11  is T or A, and X 12  is V or A; and   VH FR4 comprises a sequence according to Formula IX: WGQGTLX 1 TVSS (SEQ ID NO: 160), wherein X 1  is V or L; and/or   
       the light chain comprises one, two, three, or four framework regions selected from VL FR1, VL FR2, VL FR3, and VL FR4, wherein:
 VL FR1 comprises a sequence according to Formula X: 
 X 1 IX 2 X 3 TQSPX 4 SLX 5 X 6 SX 7 GX 8 RX 9 TIX 10 C (SEQ ID NO: 161), wherein X 1  is D or G, X 2  is Q or V, X 3  is M or L, X 4  is S or D, X 5  is S, P, or A, X 6  is A or V, X 7  is V or L, X 8  is D or E, X 9  is V or A, and X 10  is T, N, or D; 
 VL FR2 comprises a sequence according to Formula XI: WYQQKPGX 1 X 2 PKLLIK (SEQ ID NO: 162), wherein X 1  is K or Q, and X 2  is A or P; 
 VL FR3 comprises a sequence according to Formula XII: 
 GVPX 1 RFSGSGSGTDFTLTISSLQX 2 EDX 3 AX 4 YYC (SEQ ID NO: 163), wherein X 1  is S or D, X 2  is P or A, X 3  is F, L, or V, and X 4  is T or V; and 
 VL FR4 comprises a sequence according to Formula XIII: FGQGTKLEIX 1  (SEQ ID NO: 164), wherein X 1  is K or E. 
 
     
     
         9 . The antibody of any one of  claims 1 - 8 , wherein the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein:
 VH FR1 comprises a sequence selected from the group consisting of SEQ ID NOs: 2-4;   VH FR2 comprises the sequence of SEQ ID NO: 5;   VH FR3 comprises a sequence selected from the group consisting of SEQ ID NOs: 6-19; and   VH FR4 comprises a sequence selected from the group consisting of SEQ ID NOs: 20-21; and/or   
       the light chain comprises one, two, three, or four framework regions selected from VL FR1, VL FR2, VL FR3, and VL FR4, wherein:
 VL FR1 comprises a sequence selected from the group consisting of SEQ ID NOs: 22-26; 
 VL FR2 comprises a sequence selected from the group consisting of SEQ ID NOs: 27-28; 
 VL FR3 comprises a sequence selected from the group consisting of SEQ ID NOs: 29-31; and 
 VL FR4 comprises a sequence selected from the group consisting of SEQ ID NOs: 32-33. 
 
     
     
         10 . The antibody of any one of  claims 1 - 9 , wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 34-72; and/or a light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 77-101. 
     
     
         11 . The antibody of  claim 10 , wherein the antibody comprises the heavy chain variable region of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Table 13); and/or the antibody comprises the light chain variable region of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Table 14). 
     
     
         12 . The antibody of any one of  claims 1 - 11 , wherein:
 (a) the HVR-H1 comprises the amino acid sequence GYTFTDYNLH (SEQ ID NO: 105), the HVR-H2 comprises the amino acid sequence FIYPSNRITG (SEQ ID NO: 119), the HVR-H3 comprises the amino acid sequence SDVDYFDY (SEQ ID NO: 122), the HVR-L1 comprises the amino acid sequence RASQSVSTSTYSYMH (SEQ ID NO: 127), the HVR-L2 comprises the amino acid sequence YASNLES (SEQ ID NO: 135), and the HVR-L3 comprises the amino acid sequence QHSWEIPLT (SEQ ID NO: 146); or   (b) the HVR-H1 comprises the amino acid sequence GYTFTDYNLH (SEQ ID NO: 105), the HVR-H2 comprises the amino acid sequence FIYPSNQITG (SEQ ID NO: 118), the HVR-H3 comprises the amino acid sequence SDVDYFDY (SEQ ID NO: 122), the HVR-L1 comprises the amino acid sequence RASQSVSTSTYSYMH (SEQ ID NO: 127), the HVR-L2 comprises the amino acid sequence YASNLES (SEQ ID NO: 135), and the HVR-L3 comprises the amino acid sequence QHSWEIPLT (SEQ ID NO: 146).   
     
     
         13 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein:
 (a) the heavy chain variable region comprises an HVR-H1 comprising the amino acid sequence GYTFTDYNLH (SEQ ID NO: 105), an HVR-H2 comprising the amino acid sequence FIYPSNRITG (SEQ ID NO: 119), and an HVR-H3 comprising the amino acid sequence SDVDYFDY (SEQ ID NO: 122), and the light chain variable region comprises an HVR-L1 comprising the amino acid sequence RASQSVSTSTYSYMH (SEQ ID NO: 127), an HVR-L2 comprising the amino acid sequence YASNLES (SEQ ID NO: 135), and an HVR-L3 comprising the amino acid sequence QHSWEIPLT (SEQ ID NO: 146); or   (b) the heavy chain comprises an HVR-H1 comprising the amino acid sequence GYTFTDYNLH (SEQ ID NO: 105), an HVR-H2 comprising the amino acid sequence FIYPSNQITG (SEQ ID NO: 118), and an HVR-H3 comprising the amino acid sequence SDVDYFDY (SEQ ID NO: 122), and the light chain variable region comprises an HVR-L1 comprising the amino acid sequence RASQSVSTSTYSYMH (SEQ ID NO: 127), an HVR-L2 comprising the amino acid sequence YASNLES (SEQ ID NO: 135), and an HVR-L3 comprising the amino acid sequence QHSWEIPLT (SEQ ID NO: 146).   
     
     
         14 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 34-72; and/or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 77-101. 
     
     
         15 . The antibody of  claim 14 , wherein the antibody comprises the heavy chain variable region of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Table 13); and/or the antibody comprises the light chain variable region of antibody AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, or AB-64.1.15 (as shown in Table 14). 
     
     
         16 . The antibody of  claim 14  or  claim 15 , wherein:
 (a) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 59, and/or the light chain variable region comprises the amino acid sequence of SEQ ID NO: 86; or 
 (b) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 65, and/or the light chain variable region comprises the amino acid sequence of SEQ ID NO: 86. 
 
     
     
         17 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 34, 40, 42, 52, 53, and 73-76; and/or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 77, 86, and 102. 
     
     
         18 . The antibody of  claim 17 , wherein the antibody comprises the heavy chain variable region of AB-H2, AB-H9, AB-H14, AB-H15, AB-H63, AB-H64, AB-H65, or AB-H66 (as shown in Table 13); and/or the antibody comprises the light chain variable region of antibody AB-H2, AB-H9, AB-H14, AB-H15, AB-H63, AB-H64, AB-H65, or AB-H66 (as shown in Table 14). 
     
     
         19 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
 an HVR-H1 comprising a sequence according to Formula I: GX 1 X 2 X 3 TDYNX 4 H (SEQ ID NO: 186), wherein X 1  is Y or V, X 2  is T or A, X 3  is F, E, or H, and X 4  is L, F, Y, or N;   an HVR-H2 comprising a sequence according to Formula II: FIYPX 1 NX 2 IX 3 G (SEQ ID NO: 153), wherein X 1  is S or A, X 2  is G, Q, R, or V, and X 3  is T or R; and   an HVR-H3 comprising a sequence according to Formula III: SX 1 VDYFDX 2  (SEQ ID NO: 187), wherein X 1  is T, D, or F, and X 2  is Y, D, or L; and   
       wherein the light chain variable region comprises:
 an HVR-L1 comprising a sequence according to Formula IV: X 1 X 2 SQX 3 VX 4 X 5 STYSYMH (SEQ ID NO: 188), wherein X 1  is R or K, X 2  is A, G, or V, X 3  is S or D, X 4  is S, G, or H, and X 5  is T; 
 an HVR-L2 comprising a sequence according to Formula V: YX 1 X 2 X 3 X 4 X 5 S (SEQ ID NO: 189), wherein X 1  is A or E, X 2  is S or F, X 3  is N, Y, or F, X 4  is L or V, and X 5  is E or N; and 
 an HVR-L3 comprising a sequence according to Formula VI: X 1 HSX 2 X 3 X 4 PLX 5  (SEQ ID NO: 157), wherein X 1  is Q or E, X 2  is W or E, X 3  is E or A, X 4  is I or L, and X 5  is T or E. 
 
     
     
         20 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
 an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 105 and 108-114;   an HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 115-120; and   an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 121-123 and 125-126; and   
       the light chain variable region comprises:
 an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 127-128 and 130-134; 
 an HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 135 and 140-145; and 
 
       an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 146-151. 
     
     
         21 . The antibody of  claim 19  or  claim 20 , wherein the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein:
 VH FR1 comprises a sequence according to Formula VII: 
 QVQLVQSGAEVKKPGX 1 SVKX 2 SCKAS (SEQ ID NO: 158), wherein X 1  is A or S, and X 2  is V or I; 
 VH FR2 comprises the sequence of SEQ ID NO: 5; 
 VH FR3 comprises a sequence according to Formula VIII: 
 X 1 AX 2 X 3 X 4 X 5 X 6 RX 7 TX 8 TVDX 9 X 10 X 11 STX 12 YMELSSLRSEDTAVYYCAR (SEQ ID NO: 159), wherein X 1  is Y or S, X 2  is Q or E, X 3  is K or D, X 4  is F or D, X 5  is Q, F, E, or T, X 6  is G, D, or H, X 7  is V or A, X 8  is M or L, X 9  is T, N, or Q, X 10  is S or P, X 11  is T or A, and X 12  is V or A; and 
 VH FR4 comprises a sequence according to Formula IX: WGQGTLX 1 TVSS (SEQ ID NO: 160), wherein X 1  is V or L; and/or 
 
       the light chain comprises one, two, three, or four framework regions selected from VL FR1, VL FR2, VL FR3, and VL FR4, wherein:
 VL FR1 comprises a sequence according to Formula X: 
 X 1 IX 2 X 3 TQSPX 4 SLX 5 X 6 SX 7 GX 8 RX 9 TIX 10 C (SEQ ID NO: 161), wherein X 1  is D or G, X 2  is Q or V, X 3  is M or L, X 4  is S or D, X 5  is 5, P, or A, X 6  is A or V, X 7  is V or L, X 8  is D or E, X 9  is V or A, and X 10  is T, N, or D; 
 VL FR2 comprises a sequence according to Formula XI: WYQQKPGX 1 X 2 PKLLIK (SEQ ID NO: 162), wherein X 1  is K or Q, and X 2  is A or P; 
 VL FR3 comprises a sequence according to Formula XII: 
 GVPX 1 RFSGSGSGTDFTLTISSLQX 2 EDX 3 AX 4 YYC (SEQ ID NO: 163), wherein X 1  is S or D, X 2  is P or A, X 3  is F, L, or V, and X 4  is T or V; and 
 VL FR4 comprises a sequence according to Formula XIII: FGQGTKLEIX 1  (SEQ ID NO: 164), wherein X 1  is K or E. 
 
     
     
         22 . The antibody of any one of  claims 19 - 21 , wherein the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein:
 VH FR1 comprises a sequence selected from the group consisting of SEQ ID NOs: 2-4;   VH FR2 comprises the sequence of SEQ ID NO: 5;   VH FR3 comprises a sequence selected from the group consisting of SEQ ID NOs: 6-19; and   VH FR4 comprises a sequence selected from the group consisting of SEQ ID NOs: 20-21; and/or   
       the light chain comprises one, two, three, or four framework regions selected from VL FR1, VL FR2, VL FR3, and VL FR4, wherein:
 VL FR1 comprises a sequence selected from the group consisting of SEQ ID NOs: 22-26; 
 VL FR2 comprises a sequence selected from the group consisting of SEQ ID NOs: 27-28; 
 VL FR3 comprises a sequence selected from the group consisting of SEQ ID NOs: 29-31; and 
 VL FR4 comprises a sequence selected from the group consisting of SEQ ID NOs: 32-33. 
 
     
     
         23 . The antibody of any one of  claims 19 - 22 , wherein the heavy chain variable region comprises a VH FR3 comprising a sequence selected from the group consisting of SEQ ID NOs: 12-15. 
     
     
         24 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 38 and 40-72; and/or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 86-101. 
     
     
         25 . An antibody that binds to a CD33 protein, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 58 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 59 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 65 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 66 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 67 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 68 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 69 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86. 
     
     
         26 . The antibody of any one of  claims 1 - 25 , wherein the antibody is of the IgG class, the IgM class, or the IgA class. 
     
     
         27 . The antibody of  claim 26 , wherein the antibody is of the IgG class and has an IgG1, IgG2, IgG3, or IgG4 isotype. 
     
     
         28 . The antibody of  claim 27 , wherein the antibody has an IgG4 isotype, and wherein the antibody comprises an S228P amino acid substitution at residue position 228, an F234A amino acid substitution at residue position 234, and an L235A amino acid substitution at residue position 235, wherein the numbering of the residue position is according to EU numbering. 
     
     
         29 . The antibody of  claim 27 , wherein the antibody comprises one or more amino acid substitutions in the Fc region at a residue position selected from the group consisting of: C127S, L234A, L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, E345R, E430G, S440Y, and any combination thereof, wherein the numbering of the residues is according to EU or Kabat numbering. 
     
     
         30 . The antibody of  claim 29 , wherein:
 (a) the Fc region comprises an amino acid substitution at position E430G, wherein the numbering of the residue position is according to EU numbering;   (b) the Fc region comprises an amino acid substitution at positions L243A, L235A, and P331A, wherein the numbering of the residue position is according to EU numbering;   (c) the Fc region comprises an amino acid substitution at positions L243A, L235A, P331A, and E430G, wherein the numbering of the residue position is according to EU numbering;   (d) the Fc region comprises an amino acid substitution at positions K322A and E430G, wherein the numbering of the residue position is according to EU numbering;   (e) the Fc region comprises an amino acid substitution at positions P331S and E430G, wherein the numbering of the residue position is according to EU numbering;   (f) the Fc region comprises an amino acid substitution at positions A330S, P331S, and E430G, wherein the numbering of the residue position is according to EU numbering;   (g) the Fc region comprises an amino acid substitution at positions K322A, A330S, and P331S, wherein the numbering of the residue position is according to EU numbering;   (h) the Fc region comprises an amino acid substitution at positions K322A, P331S, and E430G, wherein the numbering of the residue position is according to EU numbering;   (i) the Fc region comprises an amino acid substitution at position E430G, wherein the numbering of the residue position is according to EU numbering;   (j) the Fc region comprises an amino acid substitution at positions A330S, P331S, and E430G, wherein the numbering of the residue position is according to EU numbering;   (k) the Fc region comprises an amino acid substitution at positions S267E and L328F, wherein the numbering of the residue position is according to EU numbering;   (l) the Fc region comprises an amino acid substitution at position C127S, wherein the numbering of the residue position is according to EU numbering;   (m) the Fc region comprises an amino acid substitution at positions E345R, E430G and S440Y, wherein the numbering of the residue position is according to EU numbering; or   (n) the Fc region comprises an amino acid substitution at positions L243A, L235A, and P331S, wherein the numbering of the residue position is according to EU numbering.   
     
     
         31 . The antibody of any one of  claims 1 - 30 , wherein the CD33 protein is a mammalian protein or a human protein. 
     
     
         32 . The antibody of any one of  claims 1 - 31 , wherein the CD33 protein is a wild-type protein. 
     
     
         33 . The antibody of any one of  claims 1 - 31 , wherein the CD33 protein is a naturally occurring variant. 
     
     
         34 . The antibody of any one of  claims 1 - 33 , wherein the CD33 protein is expressed on one or more cells selected from the group consisting of human dendritic cells, human macrophages, human monocytes, human osteoclasts, human neutrophils, human T cells, human T helper cell, human cytotoxic T cells, human granulocytes, and human microglia. 
     
     
         35 . The antibody of any one of  claims 1 - 34 , wherein the antibody binds specifically to a human CD33 protein. 
     
     
         36 . The antibody of any one of  claims 1 - 35 , wherein the antibody is an antibody fragment that binds to an epitope comprising amino acid residues on human CD33 or a mammalian CD33 protein. 
     
     
         37 . The antibody of any one of  claims 1 - 35 , wherein the antibody is an antibody fragment that binds to one or more human proteins selected from the group consisting of human CD33, a naturally occurring variant of human CD33, and a disease variant of human CD33. 
     
     
         38 . The antibody of  claim 36  or  claim 37 , wherein the antibody fragment is cross-linked to a second antibody fragment that binds to one or more human proteins selected from the group consisting of human CD33, a naturally occurring variant of human CD33, and a disease variant of human CD33. 
     
     
         39 . The antibody of any one of  claims 36 - 38 , wherein the fragment is an Fab, Fab′, Fab′-SH, F(ab′)2, Fv, or scFv fragment. 
     
     
         40 . The antibody of any one of  claims 1 - 39 , wherein the antibody is a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody. 
     
     
         41 . The antibody of any one of  claims 1 - 40 , wherein the antibody is a monoclonal antibody. 
     
     
         42 . The antibody of any one of  claims 1 - 40 , wherein the antibody is a bispecific antibody recognizing a first antigen and a second antigen. 
     
     
         43 . The antibody of  claim 42 , wherein the first antigen is CD33 and the second antigen is:
 (a) an antigen facilitating transport across the blood-brain-barrier;   (b) an antigen facilitating transport across the blood-brain-barrier selected from the group consisting of transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low-density lipoprotein receptor related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, a llama single domain antibody, TMEM 30(A), a protein transduction domain, TAT, Syn-B, penetratin, a poly-arginine peptide, an angiopep peptide, and ANG1005;   (c) a disease-causing agent selected from the group consisting of disease-causing peptides or proteins and disease-causing nucleic acids, wherein the disease-causing peptides or proteins are selected from the group consisting of amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, alpha-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), c9RAN protein, prion protein, PrPSc, huntingtin, calcitonin, superoxide dismutase, ataxin, ataxin 1, ataxin 2, ataxin 3, ataxin 7, ataxin 8, ataxin 10, Lewy body, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, medin, prolactin, transthyretin, lysozyme, beta 2 microglobulin, gelsolin, keratoepithelin, cystatin, immunoglobulin light chain AL, S-IBM protein, Repeat-associated non-ATG (RAN) translation products, DiPeptide repeat (DPR) peptides, glycine-alanine (GA) repeat peptides, glycine-proline (GP) repeat peptides, glycine-arginine (GR) repeat peptides, proline-alanine (PA) repeat peptides, ubiquitin, and proline-arginine (PR) repeat peptides, and the disease-causing nucleic acids are antisense GGCCCC (G2C4) repeat-expansion RNA;   (d) ligands and/or proteins expressed on immune cells, wherein the ligands and/or proteins selected from the group consisting of CD40, OX40, ICOS, CD28, CD137/4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD38, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR, LAG3, DR5, CD39, CD70, CD73, TREM1, TREM2, Siglec-5, Siglec-7, Siglec-9, Siglec-11, SirpA, CD47, CSF1-receptor, and phosphatidylserine; and   (e) a protein, lipid, polysaccharide, or glycolipid expressed on one or more tumor cells.   
     
     
         44 . The antibody of any one of  claims 1 - 43 , wherein the antibody is used in combination with one or more antibodies that specifically bind a disease-causing agent selected from the group consisting of disease-causing peptides, disease-causing proteins, amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, alpha-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), prion protein, PrPSc, huntingtin, calcitonin, superoxide dismutase, ataxin, ataxin 1, ataxin 2, ataxin 3, ataxin 7, ataxin 8, ataxin 10, Lewy body, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, medin, prolactin, transthyretin, lysozyme, beta 2 microglobulin, gelsolin, keratoepithelin, cystatin, immunoglobulin light chain AL, S-IBM protein, Repeat-associated non-ATG (RAN) translation products, DiPeptide repeat (DPR) peptides, glycine-alanine (GA) repeat peptides, glycine-proline (GP) repeat peptides, glycine-arginine (GR) repeat peptides, proline-alanine (PA) repeat peptides, ubiquitin, and proline-arginine (PR) repeat peptides, and any combination thereof; or with one or more antibodies that bind an immunomodulatory protein selected from the group consisting of: CD40, OX40, ICOS, CD28, CD137/4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD38, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR3, DR5, CD39, CD70, CD73, LAG3, TREM1, TREM2, Siglec-5, Siglec-7, Siglec-9, Siglec-11, SirpA, CD47, CSF1-receptor, phosphatidylserine, disease-causing nucleic acids, antisense GGCCCC (G2C4) repeat-expansion RNA, and any combination thereof. 
     
     
         45 . The antibody of any one of  claims 1 - 44 , wherein the antibody has a dissociation constant (K D ) for human CD33 that is at least 4-fold lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 34 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 77; at least 1-fold lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 40 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86; or at least 1-fold lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86, wherein the K D  is determined by surface plasmon resonance. 
     
     
         46 . The antibody of any one of  claims 1 - 44 , wherein the antibody has a dissociation constant (K D ) for human CD33 that ranges from about 2 nM to about 200 pM, or less than about 200 pM, and wherein the K D  is determined by BioLayer Interferometry. 
     
     
         47 . The antibody of any one of  claims 1 - 46 , wherein the antibody reduces cell surface levels of CD33. 
     
     
         48 . The antibody of  claim 47 , wherein the CD33 is expressed on the surface of human dendritic cells. 
     
     
         49 . The antibody of  claim 47  or  claim 48 , wherein the antibody reduces cell surface levels of CD33 in vitro. 
     
     
         50 . The antibody of any one of  claims 47 - 49 , wherein the antibody reduces cell surface levels of CD33 in vitro with a half maximal effective concentration (EC 50 ) that is less than 150 pM, as measured by flow cytometry. 
     
     
         51 . The antibody of any one of  claims 47 - 50 , wherein the antibody reduces cell surface levels of CD33 in vitro with an EC 50 , that is at least 50% lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 34 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 77; at least 10% lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 40 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86; at least 10% lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86; or at least 10-fold lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 103 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 104, as measured by flow cytometry. 
     
     
         52 . The antibody of any one of  claims 1 - 51 , wherein the antibody competes with one or more antibodies selected from the group consisting of AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, AB-64.1.15, AB-H2, AB-H9, AB-H14, AB-H15, AB-H63, AB-H64, AB-H65, AB-H66, and any combination thereof for binding to CD33. 
     
     
         53 . The antibody of any one of  claims 1 - 51 , wherein the antibody binds essentially the same CD33 epitope as an antibody selected from the group consisting of AB-14.1, AB-14.2, AB-14.3, AB-14.4, AB-14.5, AB-14.6, AB-14.7, AB-14.8, AB-14.9, AB-14.10, AB-14.11, AB-63.4, AB-63.5, AB-63.6, AB-63.7, AB-63.8, AB-63.9, AB-63.10, AB-63.11, AB-63.12, AB-63.13, AB-63.14, AB-63.15, AB-63.16, AB-63.17, AB-63.18, AB-64.1, AB-64.2, AB-64.3, AB-64.4, AB-64.5, AB-64.6, AB-64.7, AB-64.8, AB-64.1.1, AB-64.1.2, AB-64.1.3, AB-64.1.4, AB-64.1.5, AB-64.1.6, AB-64.1.7, AB-64.1.8, AB-64.1.9, AB-64.1.10, AB-64.1.11, AB-64.1.12, AB-64.1.13, AB-64.1.14, AB-64.1.15, AB-H2, AB-H9, AB-H14, AB-H15, AB-H63, AB-H64, AB-H65, and AB-H66. 
     
     
         54 . An antibody that binds to a CD33 protein, wherein the antibody comprises
 (a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 176 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 197 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 177 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (d) a heavy chain comprising the amino acid sequence of SEQ ID NO: 198 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (e) a heavy chain comprising the amino acid sequence of SEQ ID NO: 178 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (f) a heavy chain comprising the amino acid sequence of SEQ ID NO: 199 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (g) a heavy chain comprising the amino acid sequence of SEQ ID NO: 179 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (h) a heavy chain comprising the amino acid sequence of SEQ ID NO: 200 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 180 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (j) a heavy chain comprising the amino acid sequence of SEQ ID NO: 201 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (k) a heavy chain comprising the amino acid sequence of SEQ ID NO: 181 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (l) a heavy chain comprising the amino acid sequence of SEQ ID NO: 202 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (m) a heavy chain comprising the amino acid sequence of SEQ ID NO: 182 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (n) a heavy chain comprising the amino acid sequence of SEQ ID NO: 203 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (o) a heavy chain comprising the amino acid sequence of SEQ ID NO: 183 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (p) a heavy chain comprising the amino acid sequence of SEQ ID NO: 204 and a light chain comprising the amino acid sequence of SEQ ID NO: 185;   (q) a heavy chain comprising the amino acid sequence of SEQ ID NO: 184 and a light chain comprising the amino acid sequence of SEQ ID NO: 185; or   (r) a heavy chain comprising the amino acid sequence of SEQ ID NO: 205 and a light chain comprising the amino acid sequence of SEQ ID NO: 185.   
     
     
         55 . An isolated nucleic acid comprising a nucleic acid sequence encoding the antibody of any one of  claims 1 - 54 . 
     
     
         56 . A vector comprising the nucleic acid of  claim 55 . 
     
     
         57 . An isolated host cell comprising the vector of  claim 56 . 
     
     
         58 . A method of producing an antibody that binds to CD33, comprising culturing the cell of  claim 57  so that the antibody is produced. 
     
     
         59 . The method of  claim 58 , further comprising recovering the antibody produced by the cell. 
     
     
         60 . An isolated antibody that binds to CD33 produced by the method of  claim 58  or  claim 59 . 
     
     
         61 . A pharmaceutical composition comprising the antibody of any one of  claims 1 - 54  and a pharmaceutically acceptable carrier. 
     
     
         62 . A method of preventing, reducing risk, or treating a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, taupathy disease, infections, and cancer, comprising administering to an individual in need thereof a therapeutically effective amount of the antibody of any one of  claims 1 - 54 . 
     
     
         63 . The method of  claim 62 , wherein the disease, disorder, or injury is cancer. 
     
     
         64 . The method of  claim 62  or  claim 63 , wherein the cancer is selected from the group consisting of bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell cancer, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin's lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and multiple myeloma.