A syndrome similar to GVHD can be induced with cyclosporine (CsA) in animal models of autologous GVHD. The animal studies suggest that this syndrome generates antitumor activity similar to that seen with allogeneic GVHD. Autologous GVHD can also be induced with CsA in patients, and preliminary data suggest that this syndrome generates antitumor activity similar to that seen with allogeneic GVHD. Autologous GVHD can also produce a clinically significant antitumor effect. The mechanisms responsible for the antitumor activity of autologous GVHD will be investigated in the animal model. Specifically, the target antigens and effector cells responsible for the antitumor activity will be defined. Since autologous GVHD is a mild, self-limited disease, it should be possible to enhance the antitumor activity without increasing toxicity. Strategies for enhancing the antitumor effect of autologous GVHD, either by stimulating effector cells with IL-2, IL-4 or IL-6 or by upregulating target antigen expression with cytokines, will also be explored in the animal model. The animal results will be applied to designing studies into the mechanisms responsible for, and techniques for enhancing, the antitumor effect of autologous GVHD in an in vitro model which uses explanted tumor and effector cells from patients undergoing autologous GVHD induction. Techniques developed from the preclinical studies for enhancing the antitumor activity of autologous GVHD will be tested in clinical trials.
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