Adoptive immunotherapy of cancer with immune and activated lymphocytes: experimental and clinical studies

Abstract

Recent studies of passive adoptive immunotherapy of experimental tumors indicate that histologically different neoplasms can be cured by this procedure in mice, rats and guinea pigs. In this paper two main approaches of adoptive immunotherapy with lymphocytes are considered. One which makes use of specific tumor-immune cells and is applicable to immunogenic tumors, and the other which uses activated (allostimulated and/or IL-2-activated) lymphocytes and is applicable to immunogenic and non-immunogenic neoplasms. Experimental models of both approaches and results provided by them are reviewed. These studies indicate that transfer of tumor-reactive lymphocytes with or without the combined administration of IL-2 into syngeneic tumor-bearing animals can lead to the eradication of a disseminated neoplasia when certain conditions are met. In particular, it was found that high tumor burdens, delay of treatment and low number of transferred lymphocytes can adversely affect the results. It has also been shown that the therapeutic effect of treatment with anti-cancer drugs or irradiation may be significantly improved by the addition of adoptive immunotherapy. The successful treatment of immunogenic tumors often requires the inhibition of suppressor lymphocytes by Cy or irradiation. Non-immunogenic tumors can be successfully treated only by providing activated lymphocytes and high doses of IL-2. Recent findings of few available human studies of adoptive immunotherapy are also reviewed, and the problems of toxicity and possible therapeutic effects of infusion of autologous, activated lymphocytes and IL-2 are discussed.