Ex vivo antigen-presenting cells or activated cd-positive t cells for treatment of cancer

Abstract

This disclosure is directed to methods of preparing dendritic cells or other CD40 bearing antigen-presenting cells and methods of treating cancer by using the dendritic cells or other antigen-presenting cells in combination with anti-chemorepellant agents. This disclosure is further directed to methods of preparing T cells and methods of treating cancer, by activated T cells optionally in combination with anti-chemorepellant agents. The antigen presenting cells of the disclosure are activated by incubation with cancer cells and fusion proteins. The T cells of the disclosures are activated by incubation with activated antigen-presenting cells that were activated by incubation with cancer cells and a fusion protein. In particular, the fusion protein comprises an antigen-binding domain, e.g., an antibody or antibody fragment, and a stress protein domain.

What is claimed is: 
     
         1 . A method for preparing activated antigen-presenting cells (“APCs”), the method comprising:
 a) incubating immune cells ex vivo in presence of cancer cells and a fusion protein for a time period sufficient to produce activated APCs, wherein at least one activated APC displays an antigen derived from the cancer cells; and 
 b) isolating the activated APCs; 
 
       wherein the fusion protein comprises an antigen binding component and a stress protein component, wherein said antigen binding component binds to an antigen on one or more of the cancer cells and said stress protein component causes activation of the APCs. 
     
     
         2 . The method of  claim 1 , wherein the immune cells comprise dendritic cells, B lymphocytes, and/or mononuclear phagocytes, said mononuclear phagocytes comprising monocytes or macrophages. 
     
     
         3 . The method of  claim 1  or  2 , wherein at least one immune cell comprises a CD40 receptor. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the activated APCs comprise activated dendritic cells. 
     
     
         5 . The method of any one of  claims 1 - 4 , wherein the heat shock protein component comprises HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the antigen binding component is a single chain antibody, a variable domain, or a Fab domain. 
     
     
         8 . The method of any one of the above claims, wherein the fusion protein comprises a peptide having at least 85% sequence homology to the peptide sequence of SEQ ID NO.: 1 or SEQ ID NO.: 2. 
     
     
         9 . The method of  claim 8 , wherein the fusion protein comprises the peptide sequence of SEQ ID NO.: 2. 
     
     
         10 . The method of any one of the above claims, further comprising expanding the dendritic cells in the presence of a growth factor. 
     
     
         11 . The method of  claim 10 , wherein the growth factor is a cytokine. 
     
     
         12 . The method of  claim 10 , wherein the growth factor is selected from the group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         13 . The method of any one of  claims 1 - 12 , wherein the cancer cells are obtained from a patient. 
     
     
         14 . The method of any one of  claims 1 - 13 , wherein the cancer cells derive from breast cancer, head and neck cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, anal cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphatic cancer, pancreatic cancer, stomach cancer, mesothelioma, leukemia, lymphoma, myeloma, or thyroid cancer. 
     
     
         15 . The method of any one of  claims 1 - 14 , wherein the cancer cells derive from mesothelioma. 
     
     
         16 . The method of any one of  claims 1 - 15 , further comprising contacting the isolated activated APCs with an effective amount of an anti-chemorepellant agent. 
     
     
         17 . The method of  claim 16 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         18 . The method of  claim 16 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         19 . The method of any one of  claims 1 - 18 , wherein the immune cells are allogeneic, autologous, or derived from a cell line. 
     
     
         20 . The method of any one of  claims 1 - 19 , wherein the immune cells were collected from a patient having a tumor. 
     
     
         21 . The method of any one of  claims 1 - 20 , wherein either the activated APCs or the cancer cells are immobilized on a solid support. 
     
     
         22 . The method of  claim 21 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         23 . The method of  claim 21  or  claim 22 , wherein the activated APCs are isolated by isolating the solid support from the cancer cells and fusion protein. 
     
     
         24 . The method of  claim 2 , wherein the dendritic cells are differentiated or matured from dendritic cell precursors. 
     
     
         25 . The method of  claim 24 , wherein the dendritic cell precursors are not activated. 
     
     
         26 . The method of  claim 24 , wherein the dendritic cell precursors are free or substantially free of neutrophils, macrophages, lymphocytes, or combination thereof. 
     
     
         27 . The method of  claim 24 , wherein the dendritic cell precursors are differentiated in the presence of a growth factor. 
     
     
         28 . The method of  claim 27 , wherein the growth factor comprises a cytokine. 
     
     
         29 . The method of  claim 27 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         30 . A method for treating a cancer in a patient, the method comprising administering an effective amount of ex vivo prepared activated APCs to the patient;
 wherein the APCs were activated by incubating immune cells with cancer cells and a fusion protein, wherein the fusion protein comprises a target binding component and a heat shock protein component, wherein said target binding component binds to the cancer cells and said heat shock protein component causes activation of the immune cells.   
     
     
         31 . The method of  claim 30 , wherein the immune cells comprise dendritic cells, B lymphocytes, or mononuclear phagocytes, said mononuclear phagocytes comprising monocytes or macrophages. 
     
     
         32 . The method of any one of  claim 30  or  31 , wherein the immune cell comprises a CD40 receptor. 
     
     
         33 . The method of any one of  claims 30 - 32 , wherein the immune cells comprise dendritic cells. 
     
     
         34 . The method of any one of  claims 30 - 33 , further comprising administering to the patient an effective amount of an anti-chemorepellant agent. 
     
     
         35 . The method of any one of  claims 30 - 34 , wherein the APCs have an anti-chemorepellant agent bound thereto via one or more cell surface receptors. 
     
     
         36 . The method of  claim 35 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         37 . The method of  claim 36 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         38 . The method of any one of  claims 30 - 37 , wherein the heat shock protein component comprises HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         39 . The method of  claim 38 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         40 . The method of any one of  claims 30 - 38 , wherein the target binding component comprises a single chain antibody, a variable domain, or a Fab domain. 
     
     
         41 . The method of any one of  claims 30 - 40 , wherein the fusion protein comprises a peptide having at least 85% sequence homology to the peptide sequence of SEQ ID NO.: 1 or SEQ ID NO.: 2. 
     
     
         42 . The method of  claim 41 , wherein the fusion protein comprises the peptide sequence of SEQ TD NO.: 2. 
     
     
         43 . The method of any one of  claims 30 - 42 , further comprising expanding the dendritic cells in presence of a growth factor. 
     
     
         44 . The method of  claim 43 , wherein the growth factor is a cytokine. 
     
     
         45 . The method of  claim 43 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         46 . The method of any one of  claims 30 - 45 , wherein the cancer cells are obtained from the patient. 
     
     
         47 . The method of any one of  claims 30 - 46 , wherein the cancer cells derive from breast cancer, head and neck cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, anal cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphatic cancer, pancreatic cancer, stomach cancer, or thyroid cancer. 
     
     
         48 . The method of any one of  claims 30 - 47 , wherein the cancer cells derive from mesothelioma. 
     
     
         49 . The method of any one of  claims 30 - 48 , wherein the APCs are allogeneic, autologous, or derived from a cell line. 
     
     
         50 . The method of any one of  claims 30 - 49 , wherein the APCs are collected from a patient having a tumor. 
     
     
         51 . The method of any one of  claims 30 - 50 , wherein either the APCs or the cancer cells are immobilized on a solid support. 
     
     
         52 . The method of  claim 51 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         53 . The method of  claim 31 , wherein the dendritic cells are differentiated or matured from dendritic cell precursors. 
     
     
         54 . The method of  claim 53 , wherein the dendritic cell precursors are not activated. 
     
     
         55 . The method of  claim 53 , wherein the dendritic cell precursors are free or substantially free of neutrophils, macrophages, lymphocytes, or combination thereof. 
     
     
         56 . The method of  claim 53 , wherein the dendritic cell precursors are differentiated in the presence of a growth factor. 
     
     
         57 . The method of  claim 56 , wherein the growth factor comprises a cytokine. 
     
     
         58 . The method of  claim 56 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         59 . A method for treating a cancer in a patient, the method comprising:
 a) incubating dendritic cells in the presence of cancer cells and a fusion protein ex vivo for a time period sufficient to produce antigen-presenting dendritic cells, wherein at least one antigen-presenting dendritic cell displays an antigen derived from the cancer cells;   b) isolating the antigen-presenting dendritic cells; and   c) administering an effective amount of the antigen-presenting dendritic cells to the patient;   
       wherein the fusion protein comprises a antigen binding component and a stress protein component, wherein said antigen binding component binds to the cancer cells and said stress protein component causes activation of dendritic cells. 
     
     
         60 . The method of  claim 59 , wherein the antigen-presenting dendritic cells have an anti-chemorepellant agent bound thereto via one or more cell surface receptors. 
     
     
         61 . The method of  claim 59  or  claim 60 , further comprising administering to the patient an effective amount of an anti-chemorepellant agent. 
     
     
         62 . The method of  claim 61 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         63 . The method of  claim 61 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         64 . The method of any one of  claims 59 - 63 , wherein the heat shock protein component comprises HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         65 . The method of  claim 64 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         66 . The method of any one of  claims 59 - 65 , wherein the antigen binding component comprises a single chain antibody, a variable domain, or a Fab domain. 
     
     
         67 . The method of any one of  claims 59 - 66 , further comprising expanding the dendritic cells in presence of a growth factor. 
     
     
         68 . The method of  claim 67 , wherein the growth factor is a cytokine. 
     
     
         69 . The method of  claim 67 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         70 . The method of any one of  claims 59 - 69 , wherein the cancer cells are obtained from the patient. 
     
     
         71 . The method of any one of  claims 59 - 70 , wherein the dendritic cells are allogeneic, autologous, or derived from a cell line. 
     
     
         72 . The method of any one of  claims 59 - 71 , wherein the dendritic cells are collected from a patient having a tumor. 
     
     
         73 . The method of any one of  claims 59 - 72 , wherein either the dendritic cells or the cancer cells are immobilized on a solid support. 
     
     
         74 . The method of  claim 73 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         75 . The method of any one of  claims 59 - 74 , wherein the dendritic cells are differentiated or matured from dendritic cell precursors. 
     
     
         76 . The method of  claim 75 , wherein the dendritic cell precursors are not activated. 
     
     
         77 . The method of  claim 75 , wherein the dendritic cell precursors are free or substantially free of neutrophils, macrophages, lymphocytes, or combination thereof. 
     
     
         78 . The method of  claim 75 , wherein the dendritic cell precursors are differentiated in the presence of a growth factor. 
     
     
         79 . The method of  claim 78 , wherein the growth factor comprises a cytokine. 
     
     
         80 . The method of  claim 78 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         81 . An ex vivo composition comprising immune cells and an effective amount of a fusion protein, said fusion protein comprising a cancer cell binding component and a stress protein component. 
     
     
         82 . The composition of  claim 81 , wherein the immune cells comprise dendritic cells, B lymphocytes, and/or mononuclear phagocytes. 
     
     
         83 . The composition of  claim 81  or  82 , wherein at least one immune cell expresses a CD40 receptor. 
     
     
         84 . The composition of any one of  claims 81 - 83 , wherein the immune cells are activated APCs. 
     
     
         85 . The composition of any one of  claims 81 - 84 , wherein the activated APCs comprise activated dendritic cells. 
     
     
         86 . The composition of any one of  claims 81 - 85 , further comprising a growth factor. 
     
     
         87 . The composition of  claim 86 , wherein the growth factor comprises a cytokine. 
     
     
         88 . The composition of  claim 86 , wherein the growth factor is selected from a group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         89 . A pharmaceutical composition comprising activated antigen presenting cells (APCs) and an anti-chemorepellant agent. 
     
     
         90 . The composition of  claim 89 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         91 . The composition of  claim 89 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         92 . The composition of any one of  claims 89 - 91 , wherein the activated APCs comprise activated dendritic cells. 
     
     
         93 . The composition of any one of  claims 89 - 92 , further comprising a pharmaceutically acceptable excipient. 
     
     
         94 . A ex vivo container comprising a composition comprising immune cells and an effective amount of a fusion protein, said fusion protein comprising a cancer cell binding component and a stress protein component, wherein the container can be maintained under reproducible, controlled conditions. 
     
     
         95 . A method for preparing activated T cells, the method comprising:
 a) providing activated antigen-presenting cells (APCs) that were activated in the presence of cancer cells and a fusion protein ex vivo for a time period sufficient to produce activated antigen-presenting cells, wherein at least one activated antigen-presenting cell displays an antigen derived from the cancer cells;   b) contacting the activated antigen-presenting cells with T cells for a period of time sufficient to activate the T cells; and   c) isolating the activated T cells.   
     
     
         96 . The method of  claim 95 , wherein the fusion protein comprises a cancer cell binding component and a heat shock protein component, wherein said cancer cell binding component binds to the cancer cells and said heat shock protein component causes activation of antigen-presenting cells. 
     
     
         97 . The method of  claim 96 , wherein the heat shock protein component comprises HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         98 . The method of  claim 97 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         99 . The method of any one of  claims 96 - 98 , wherein the cancer cell binding component is a single chain antibody, a variable domain, or a Fab domain. 
     
     
         100 . The method of any one of  claims 95 - 99 , wherein the APCs are selected from the group consisting of dendritic cells, B lymphocytes, mononuclear phagocytes, and any combination thereof. 
     
     
         101 . The method of  claim 100 , wherein the APCs are dendritic cells and further comprising expanding the dendritic cells in presence of a growth factor. 
     
     
         102 . The method of  claim 101 , wherein the growth factor is a cytokine. 
     
     
         103 . The method of  claim 101 , wherein the growth factor is selected from the group consisting of Flt-3 ligand, GM-CSF, IL-4, M-CSF, IFNα, IL-1β, IL-4, IL-6, IL-13, IL-15 and TNFα. 
     
     
         104 . The method of any one of  claims 95 - 103 , wherein the cancer cells are obtained from a patient. 
     
     
         105 . The method of any one of  claim 95 - 104 , further comprising contacting the isolated activated T cells with an effective amount of an anti-chemorepellant agent. 
     
     
         106 . The method of  claim 105 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         107 . The method of  claim 105 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         108 . The method of any one of  claims 95 - 107 , wherein the APCs and/or T cells are allogeneic, autologous, or derived from a cell line. 
     
     
         109 . The method of any one of  claims 95 - 107 , wherein the APCs and/or the T cells are isolated from a patient having cancer. 
     
     
         110 . The method of any one of  claims 95 - 109 , wherein the activated APCs are immobilized on a solid support. 
     
     
         111 . The method of  claim 110 , wherein the activated T cells are isolated by removing the solid support from the T cells. 
     
     
         112 . The method of any one of  claims 95 - 109 , wherein the T cells are immobilized on a solid support. 
     
     
         113 . The method of  claim 112 , wherein the activated T cells are isolated by isolating the solid support from the APCs. 
     
     
         114 . The method of any one of  claims 110 - 113 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         115 . A method for treating a cancer in a patient, the method comprising administering an effective amount of activated T cells to the patient, wherein the activated T cells were prepared by:
 incubating antigen-resenting cells (APCs) with tumor cells and a fusion protein for a period of time sufficient to activate the APCs; and   contacting the activated APCs with T cells for a period of time sufficient to activate the T cells.   
     
     
         116 . The method of  claim 115 , further comprising administering to the patient an effective amount of an anti-chemorepellant agent. 
     
     
         117 . The method of  claim 116 , wherein the T cells have an anti-chemorepellant agent bound thereto via one or more cell surface receptors. 
     
     
         118 . The method of  claim 116  or  117 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC  651016 , thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         119 . The method of  claim 118 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         120 . The method of any one of  claims 115 - 119 , wherein the fusion protein comprises a heat shock protein component comprising HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         121 . The method of  claim 120 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         122 . The method of any one of  claims 115 - 121 , wherein the fusion protein comprises a cancer cell binding component comprising a single chain antibody, a variable domain, or a Fab domain. 
     
     
         123 . The method of any one of  claims 115 - 122 , wherein the cancer cells are obtained from the patient. 
     
     
         124 . The method of any one of  claims 115 - 122 , wherein the APCs are allogeneic, autologous, or derived from a cell line. 
     
     
         125 . The method of any one of  claims 95 - 123 , wherein the APCs are collected from the patient. 
     
     
         126 . The method of any one of  claims 95 - 125 , wherein the T cells are allogeneic, autologous, or derived from a cell line. 
     
     
         127 . The method of any one of  claims 95 - 125 , wherein the T cells are collected from the patient. 
     
     
         128 . The method of any one of  claims 95 - 127 , wherein either the activated APCs or the T cells are immobilized on a solid support. 
     
     
         129 . The method of  claim 128 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         130 . The method of any one of  claims 95 - 129 , wherein the APCs are dendritic cells, and the dendritic cells are differentiated or matured from dendritic cell precursors. 
     
     
         131 . A method for treating a cancer in a patient, the method comprising:
 a) providing activated APCs that were activated by incubating APCs in the presence of cancer cells and a fusion protein ex vivo for a time period sufficient to produce activated APCs, wherein at least one activated APC displays an antigen derived from the cancer cells;   b) contacting the activated APCs with T cells for a period of time sufficient to activate the T cells;   e) isolating the activated T cells; and   d) administering an effective amount of the activated T cells to the patient.   
     
     
         132 . The method of  claim 131 , wherein the activated T cells have an anti-chemorepellant agent bound thereto via one or more cell surface receptors. 
     
     
         133 . The method of  claim 131  or  claim 132 , further comprising administering to the patient an effective amount of an anti-chemorepellant agent. 
     
     
         134 . The method of any one of  claims 131 - 133 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         135 . The method of  claim 134 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         136 . The method of any one of  claims 131 - 135 , wherein the fusion protein comprises a heat shock protein component comprising HSP70 or an immune activating fragment and/or modified sequence thereof. 
     
     
         137 . The method of  claim 136 , wherein the HSP70 or the immune activating fragment and/or modified sequence thereof is from  Mycobacterium tuberculosis.    
     
     
         138 . The method of any one of  claims 131 - 137 , wherein the fusion protein comprises a cancer cell binding component comprising a single chain antibody, a variable domain, or a Fab domain 
     
     
         139 . The method of any one of  claims 131 - 138 , wherein the cancer cells are obtained from the patient. 
     
     
         140 . The method of any one of  claims 131 - 139 , wherein the APCs are allogeneic, autologous, or derived from a cell line. 
     
     
         141 . The method of any one of  claims 131 - 139 , wherein the APCs are collected from the patient. 
     
     
         142 . The method of any one of  claims 131 - 141 , wherein the T cells are allogeneic, autologous, or derived from a cell line. 
     
     
         143 . The method of any one of  claims 131 - 141 , wherein the T cells are collected from the patient. 
     
     
         144 . The method of any one of  claims 131 - 143 , wherein the T cells or APCs are immobilized on a solid support. 
     
     
         145 . The method of  claim 144 , wherein the solid support comprises a surface of a column, a sepharose bead, a gel, a matrix, a magnetic bead, or a plastic surface. 
     
     
         146 . The method of any one of  claims 115 - 145 , further comprising selecting a patient having a cancer which exhibits a chemorepellant effect. 
     
     
         147 . The method of  claim 146 , wherein the cancer overexpresses CXCL12. 
     
     
         148 . The method of any one of  claims 115 - 147 , wherein the cancer comprises breast cancer, head and neck cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, anal cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphatic cancer, pancreatic cancer, stomach cancer, mesothelioma, leukemia, lymphoma, myeloma, or thyroid cancer. 
     
     
         149 . A pharmaceutical composition comprising activated T cells and an anti-chemorepellant agent. 
     
     
         150 . The composition of  claim 149 , wherein the anti-chemorepellant agent is selected from the group consisting of AMD3100 or a derivative thereof, AMD11070, AMD12118, AMD11814, AMD13073, FAMD3465, C131, BKT140, CTCE-9908, KRH-2731, TC14012, KRH-3955, BMS-936564/MDX-1338, LY2510924, GSK812397, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, tannic acid, NSC 651016, thalidomide, GF 109230X, an antibody that interferes with dimerization of a chemorepellant chemokine, and an antibody that interferes with dimerization of a receptor for a chemorepellant chemokine. 
     
     
         151 . The composition of  claim 149 , wherein the anti-chemorepellant agent is AMD3100. 
     
     
         152 . The composition of any one of  claims 149 - 151 , further comprising a pharmaceutically acceptable excipient. 
     
     
         153 . The composition of any one of  claims 149 - 152 , further comprising a fusion protein. 
     
     
         154 . The composition of any one of  claims 149 - 153 , wherein the activated T cells were activated by the method of any one of  claims 1 - 20 . 
     
     
         155 . A composition comprising a complex comprising an activated antigen presenting cell (APC), a fusion protein, and a T cell, wherein the fusion protein comprises a cancer binding component and a stress protein component. 
     
     
         156 . The composition of  claim 155 , wherein the T cell is activated by the interaction with the activated APC.