Dual-specific T cells combine proliferation and antitumor activity.
An effective immune response against cancer requires the activation and expansion of specific T cells. Tumor antigens, however, are generally poor immunogens. To achieve expansion of tumor-reactive T cells in vivo, we used a strategy of generating dual-specific T cells that could respond to a powerful immunogen while also possessing tumor reactivity. We generated dual-specific T cells by genetic modification of alloreactive T cells with a chimeric receptor recognizing folate-binding protein, an ovarian cancer-associated antigen. Mouse dual-specific T cells responded in vitro to both allogeneic antigen and tumor cells expressing folate-binding protein, and expanded in number in vivo in response to immunization with allogeneic cells. Most importantly, the combination of dual-specific T cells and immunization had an antitumor effect in vivo. We also generated human dual-specific T cells and characterized the dual-specific nature of individual clones. Assigning the tasks of expansion and tumor reactivity to different receptors within the same lymphocyte may help to overcome the problem of poor immunogenicity of tumor antigens.
Kershaw
Michael H
MH
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Westwood
Jennifer A
JA
Hwu
Patrick
P
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002277:Carcinoma / Q000276:immunology / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002455:Cell Division; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012509:Sarcoma / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins