Therapeutic Use of Antimelanoma Monoclonal Antibodies

Monoclonal antibodies (MAb) to tumor-associated antigens are attracting much attention for tumor therapy. Melanomas belong to the tumors most studied in this respect, and several melanoma-associated antigens have been studied in great detail. These include the melanoma-associated glycoprotein p97, the melanoma-associated proteoglycan, and glycolipid antigens. Although none of the antigens is absolutely specific for tumor, the degree of relative specificity appears to be sufficient to use several of the melanoma antigens as therapeutic “targets”. Antimelanoma MAb can be applied therapeutically in several ways. The most straightforward approach is use of MAb without further modification. MAb which kill melanoma cells in the presence of human serum as the source of complement or mediate antibody-dependent cellular cytotoxicity with human natural killer (NK) cells or macrophages as effectors are logical choices for this. Some cases of partial or even complete regression of metastatic melanoma have been observed in patients treated with such MAb. Combinations of such MAb with interleukin 2 (IL-2) or other immunological response modifiers are of great interest. Alternatively, one may use antimelanoma MAb (or fragments prepared from MAb) as carriers of antitumor agents, including radioactive isotopes, toxins, or chemotherapeutic drugs. Although it is premature to make any conclusions about the efficacy of such conjugates, we are optimistic that it will be feasible by using the right combination of MAb and antitumor agent to achieve therapeutic benefit. Another approach is to develop therapeutic “vaccines” for active immunization, once an antigen characterized by using a MAb has proven to have a relatively high level of tumor selectively. Anti-idiotypic antibodies and live recombinant viruses inducing tumor antigen expression in infected cells provide alternative strategies to this approach.