GENERATION OF CYTOTOXIC EFFECTOR-CELLS AGAINST HUMAN-MELANOMA

Metastatic or tumor-draining lymph nodes from six of nine melanoma pat ients undergoing lymph node dissection for metastatic melanoma generat ed cytotoxic T cells against autologous melanoma when these lymph node cells were treated by in vitro sensitization and recombinant interleu kin-2 (IL-2). During the initial lymphocyte culture (2-6 weeks), cross -reactivity with autologous tumor cells, K562 and Daudi cells was usua lly noted. Cold-target inhibition assay with K562 and Daudi showed K56 2/Daudi-associated antigens on melanoma cells. During the later phase of lymphocyte culture with repeated in vitro sensitization (over 6-10 weeks), cytotoxicity was noted against autologous and allogeneic melan oma cells but not against K562, Daudi cells or autologous fibroblasts. Repeated in vitro sensitization resulted in the selection of specific cytotoxic lymphocytes against melanoma. Cold-target inhibition assay with autologous and allogeneic melanoma cells revealed shared and indi vidual antigens. Using blocking monoclonal antibodies, MHC-restricted killing was noted in the autologous system. Further, both the autologo us and allogeneic systems could be mediated through adhesion molecules such as ICAM-1 and LFA-3 on melanoma cells and LFA-1 on T cells. This study suggests that a constellation of cytotoxic effector cells and m elanoma-associated antigens map be pivotal in tumor killing. Thus, fut ure adoptive immunotherapy should modulate and enhance this complex in teraction.