Recruitment of inflammatory cells to a tumor deposit potentiates the immunotherapeutic effects of interleukin-2

Abstract

Interleukin-2 (IL-2) is a potent immunotherapeutic agent in murine models of intraperitoneal, pulmonary, and hepatic tumor implantation. Because of the systemic toxicity documented at doses of IL-2 required to control tumor growth, potentiation of the effects of low dose IL-2 is an important problem in immunotherapy. To address this problem, we attempted to recruit lymphocytes into a tumor mass. Allogeneic P185 (H-2d) tumor was mixed with MCA-105 (H-2b) tumor and injected s. c. into C57BL/6 (H-2b) mice. Mice were treated with 50,000 units of IL-2 twice daily from day 0 to day 6. When IL-2 alone was used to treat s. c. tumor, there was no reduction in the size of tumor implants. When allogeneic tumor was mixed with syngeneic tumor, there was a reduction in tumor size at the high dose of allogeneic tumor but not at the low dose. When allogeneic tumor was mixed with syngeneic tumor and the mice treated with IL-2, the immunotherapeutic effects of IL-2 were markedly increased. These studies show that an immune response to alloantigens, generated within tumor tissue can augment the immunotherapeutic effects of exogenous IL-2.

Intraperitoneal Chemotherapy and Immunotherapy

“…IL-2 + LAK therapy was effective in irradiated mice as well as in immunedeficient nude mice [90][91]. Moreover, IL-2 + LAK therapy had synergistic antitumor effects when combined with cyclophosphamide [93], Antitumor effects could also be augmented by initiating an inflammatory response at the tumor site and by augmenting LAK lysis through the mecha nism of antibody dependent cellular cytotoxicity (ADCC) by the addition of monoclonal antibodies [94][95][96]. Concurrent alloimmune responses [97.…”