IMMUNOCYTOKINES - A PROMISING APPROACH TO CANCER-IMMUNOTHERAPY

Recombinant antibody cytokine fusion proteins are immunocytokines that achieve high cytokine concentrations in the tumor microenvironment an d thereby effectively stimulate cellular immune responses against mali gnancies. The activation and expansion of immune effector cells, such as CD8(+) T lymphocytes, by interleukin-2 immunocytokines resulted in the eradication of established pulmonary and hepatic metastases of mur ine melanoma and colorectal carcinoma in syngeneic mouse models. These immunocytokines were equally effective in eliminating established bon e marrow and liver metastases of murine neuroblastoma by activating na tural killer cells. The effective eradication of metastases by immunoc ytokines resulted in significant prolongation in life span of mice ove r that of controls receiving equivalent mixtures of antibody and inter leukin-2, which failed to reduce the growth of disseminated metastases . Proof of concept was established, indicating that immunocytokine-ind uced activation and expansion of immune effector cells in the tumor mi croenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clini cal applications that improve treatment of cancer patients with minima l residual disease in an adjuvant setting. PHARMACOL. THER. 80(3):277- 292 1998, (C) 1998 Elsevier Science Inc.