Potential uses of interleukin 2 in cancer therapy.
Interleukin 2 (IL 2) has several potential uses in cancer therapy including: the augmentation of specific T cell mediated anti-tumor immunity and the activation of non-specific cytolytic effector cells, termed lymphokine-activated killer (LAK) cells. The current review will present data from our laboratory demonstrating in animal models the feasibility of both potential approaches. Studies to be reviewed show that: IL 2 can induce the proliferation and expansion in number of tumor-reactive T cells in vitro; T cells grown in culture in IL 2 can be effective reagents in vivo for specific tumor therapy; the administration of exogenous IL 2 can induce the growth and augment the function of cultured T cells in vivo; however, as a corollary, T cells cultured long-term in vivo with IL 2 are functionally limited in vivo without the administration of exogenous IL 2 in vivo; by contrast, T cells grown in vitro with specific antigen, as opposed to IL 2, as the major stimulus for proliferation are able to proliferate rapidly in vivo, distribute widely in host lymphoid organs, and mediate therapy of disseminated murine leukemia; importantly, such antigen-driven long-term cultured T cells can survive long-term in vivo and provide specific immunologic memory, and, the administration of low-dose IL 2 in vivo can induce the growth of antigen-driven long-term cultured T cells in vivo and thereby increase the number of functional memory T cells; the culture of lymphoid cells in high concentrations of IL 2 can induce LAK cells in vitro capable of lysing leukemia in vitro; LAK cells generated in vitro can mediate a small but detectable anti-tumor effect in vivo against disseminated leukemia as an adjunct to chemotherapy; and, high-dose IL 2 administered in vivo can activate LAK cells in vivo and cure disseminated murine leukemia. Therefore, it is highly likely that IL 2 can become an effective reagent for the therapy of human cancer.
D000818:Animals; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D007116:Immunization, Passive; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy; D007942:Leukemia, Experimental / Q000628:therapy*; D008213:Lymphocyte Activation; D008657:Metabolic Clearance Rate; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D003520:Cyclophosphamide