IMMUNOCYTOKINES - A NEW APPROACH TO IMMUNOTHERAPY OF MELANOMA

Targeted interleukin-2 (IL-2) therapy with immunocytokines (i.e. antib ody-cytokine fusion proteins) is effective in eradicating established hepatic and pulmonary metastases of melanoma in animal model systems. The effector mechanisms responsible for this antitumor effect in synge neic, immunocompetent mice involves mainly CD8+T cells. This was clear ly indicated by immunohistochemical analyses, in vivo depletion studie s and cytotoxicity tests. Such CD8+T cells, isolated from tumor-bearin g mice after immunocytokine therapy, exerted a major histocompatibilit y complex class I-restricted cytotoxicity against the same tumor in vi tro. Because of this cellular immune response, antibody-directed IL-2 therapy can even address established metastases displaying extensive h eterogeneity in the expression of the targeted antigen. The effector m echanisms induced by immunocytokines facilitate partial regressions of large subcutaneous melanoma exceeding more than 5% of the body weight . These results demonstrate the ability of immunocytokines to induce a T-cell-dependent host immune response capable of eradicating establis hed melanoma metastases in clinically relevant organs and offers an ef fective, new tool for immunotherapy of malignant melanoma.