Potential for specific cancer therapy with immune T lymphocytes

Abstract

In animal models, advanced disseminated tumors can be specifically eradicated by infusions of T lymphocytes immune to tumor. The most successful regimens require a relatively small tumor burden and immunosuppression of the host to augment the transfer of immunity. Since chemotherapeutic agents administered to tumor-bearing hosts can achieve both requirements, models that combine chemotherapy and immune cells have been developed and have been shown to be effective for the therapy of advanced syngeneic malignancies. Surprisingly, tumor eradication in these and similar models does not require the transfer of cytotoxic T lymphocytes. Rather, noncytotoxic T cells of the helper/inducer subset alone are sufficient, presumably mediating tumor elimination by a delayed-type hypersensitivity mechanism involving induction of host inflammatory cells. Since donor T cells must persist in the host to provide maximum benefit in therapy, the outcome of therapy is subject to both positive and negative influences within the host for a prolonged period of time. Interleukin-2 (IL-2), a T cell replication-inducing lymphokine, promotes the in vitro growth of antigen-activated T lymphocytes. T lymphocytes immune to tumor can be grown long-term in vitro in response to IL-2 and are able to mediate a specific, cell dose-dependent effect in therapy when inoculated into tumor-bearing hosts. In vitro such long-term cultured T lymphocytes are exquisitely dependent upon exogenous IL-2 for the induction of proliferation and survival. In vivo the administration of IL-2 induces the growth of similar long-term cultured T lymphocytes and, as a consequence, increases their therapeutic efficacy. Therefore, IL-2 can be utilized both in vitro and in vivo to augment specific T cell responses for the therapy of established tumors.