Carcinoma by Monoclonal Antibodies against Human Small Cell Lung Augmentation of Lymphokine-activated Killer Cell Cytotoxicity

This study examined the lymphokine-activated killer (LAK) cell cytotoxicity on monoclonal antibody (MoAb)-bound tumor cells from the human small cell lung carcinoma cell lines H69 and H128. LAK cells were generated from normal peripheral blood mononuclear cells by incubation with interleukin 2 for 3 or more days. Cells from the LAK culture were cytotoxic to natural killer-sensitive (KS62,84% cytotoxicity) and natural killer-resistant (Daudi, 85%; H69 and H128,69% and 97%, respectively) cell lines, and to freshly excised human lung (49%) and breast (57%) tumors. LAK cytotoxicity to H69 or H128 cells was significantly augmented by target cell preincubation with the small cell lung carcinoma-reactive MoAbs 1096 (increases of up to 271%) or 5023 (up to 223%). SO X"5023 or 1096 did not enhance LAK cytotoxicity to Daudi cells of lymphoblastoid origin. Pretreatment of LAK cells with an anti-He receptor antibody blocked MoAb augmentation by 1096 or 5023 (but not LAK cytotoxicity), suggesting that LAK-MoAb interaction may be mediated by Fc binding. LAK activity coincided with emergence of a large cell (interleukin 2-stimulated large mononuclear leukocyte ( IMl ,)| subset expressing the CD 16 and NKII-I surface determinants. Serial immunophenotyping of the LAK cell culture harvested at Days 3, 5, and 7 indicated that the level of LAK cytotoxicity, with or without MoAb augmentation, correlated with frequency of NKH-1-reactive I.MLs. These observations support the hypothesis that LAK cytotoxicity is mediated by a NKH-1 -reactive IMI subpopulation. Antitumor cytotox icity may be augmented by tumor-reactive MoAbs through Fc binding to