BIOLOGIC THERAPY OF MELANOMA WITH CYTOKINES AND LYMPHOCYTES

Melanoma has a somewhat unpredictable behavior, and spontaneous regres sions do occasionally occur. Many have surmised that these are the res ult of immunologic attack by the host. Immunologic treatment has been more successful for melanoma than for most other neoplasms, even with relatively crude therapies, such as bacterial products. With the avail ability of recombinant cytokines, immunotherapy for melanoma has enter ed a new era. Interleukin-2 (IL-2), which acts entirely through immuno logic mechanisms, has been tested extensively, either alone, in combin ation with other cytokines, or with adoptive cellular therapy. Alone, it has only modest antitumor activity, even at high doses. Its utility may be greater when combined with immunocompetent cells, especially t umor-sensitized T lymphocytes, in adoptive immunotherapy. On the other hand, nonspecific lymphokine-activated killer (LAK) cells do not appe ar to add significantly to the efficacy of IL-2 alone. Interferon-gamm a (IFN-gamma) also has had fairly limited activity in the advanced dis ease setting, but, on the basis of a recently completed randomized tri al, has arguably become the ''standard of care'' in the adjuvant setti ng for patients with high-risk melanoma, particularly node-positive pa tients. A number of regimens combining IL-2, IFN-gamma, and chemothera peutic agents have yielded striking response rates in small trials and await conformation in larger studies. With better delineation of the host immune response and definition of relevant tumor antigens, we can look forward to exciting results with combinations of vaccines, cytok ines, and adoptive cellular approaches, particularly in patients with micrometastatic disease. (C) 1996 Wiley-Liss, Inc.