Rationale for Immunocytokines

As fusion proteins combining monoclonal antibodies with cytokines, immuno-cytokines were developed to improve upon the benefit:risk ratios of monoclonal antibodies and cytokines alone or as combination therapy. Immunocytokines are hypothesized to confer two possible advantages over currently available immunotherapies (3). First, by providing both antibody effector activities and a cytokine cosignal for the generation of cytotoxic cellular immunity, immunocytokines may amplify antitumor immune responses relative to those obtained with current immunotherapies. Second, by targeting delivery of cytokines to the tumor microenvironment, immunocytokines deliver biologically active concentrations of cytokines at lower and less toxic doses than are required by systemic cytokine therapy. Data from in vitro studies and in vivo tumor models have borne out these hypotheses by showing that immunocytokines stimulate tumor-suppress-

tumor cell death

Fig. 1. Hypothesized mechanisms of antitumor action of immunocytokines.

tumor cell death

Fig. 1. Hypothesized mechanisms of antitumor action of immunocytokines.

ing immune responses and that in vivo administration of immunocytokines causes a greater antitumor effect than administration of a mixture of an equivalent dose of antibody and cytokine. Immunocytokines also appear to prolong cytokine biological activity relative to that of systemically administered cytokines.

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