ANTITUMOR EFFECTS OF INTERLEUKIN-7 AND ADOPTIVE IMMUNOTHERAPY ON HUMAN COLON-CARCINOMA XENOGRAFTS

The antitumor properties of recombinant human IL-7 (rhIL-7) on a human tumor was evaluated by engrafting a human colon carcinoma into immuno deficient mice and then treating the mice with rhIL-7 and adoptively t ransferred human peripheral blood T cells. It was found that rhIL-7 al one had no effect on the survival of the tumor-bearing recipients. How ever, the combination of rhIL-7 and human T cells significantly promot ed the survival of the recipients compared with mice receiving either treatment by itself. When the surviving mice were analyzed 6 mo later for the degree of human cell engraftment, the recipients receiving bot h rhIL-7 and human T cells had greater numbers of human CD8+ T cells i n the spleens. However, the human T cells recovered from the surviving mice showed low lytic activity against the tumor in vitro. Supernatan ts from human T cells cultured with the tumor and rhIL-7 in vitro were found to inhibit tumor growth and were demonstrated to contain high l evels of IFN-gamma. Antibodies to IFN-gamma neutralized the growth inh ibition of the tumor both in vitro and in vivo demonstrating that the in vivo mechanism underlying the antitumor effects of this regimen was partly dependent on the production of IFN-gamma by the T cells and no t their cytolytic capability. Interestingly, systemic administration o f rhIFN-gamma to tumor-bearing mice yielded little antitumor effect su ggesting that adoptive immunotherapy with rhIL-7 was superior possibly because of the continuous local release of the cytokines. Therefore, rhIL-7 may be of clinical use as an antineoplastic agent and the human /mouse model is a potentially important preclinical model for in vivo evaluation of the efficacy of this and other immunotherapies.