Potentiation of long-term-cultured lymphokine-activated killer cell cytotoxicity against small-cell lung carcinoma by anti-CD3 x anti-(tumor-associated antigen) bispecific antibody

Abstract

Lymphokine-activated killer (LAK) cells exhibit a potent cytotoxicity to malignant cells in vitro. However, a satisfactory effect has not been obtained in many clinical studies except for a few cases. One of the most important reasons why cytolytic activity could not be exhibited in vivo is that LAK cells do not accumulate in the tumor tissue because of a lack of specificity. In the present study, we show the effect of a bispecific antibody (bsAb) on the accumulation of LAK cells around the small-cell lung carcinoma (SCLC) cell and the subsequent enhancement of LAK cell cytotoxicity against SCLC. When short-term(4 days)-cultured LAK cells were used, OKT3 x LU246 bsAb, which direct CD3+ T-LAK cells to the target cell, induced a similar level of cytotoxicity to that induced by 3G8 x LU246 bsAb, which directs CD16+ LAK cells. Long-term(21 days)-cultured LAK cells exhibited a reduced spontaneous cytotoxicity but retained high cytotoxic activity, which could be directed by OKT3 x LU246 or 3G8 x LU246 bsAb. The inhibitory effect of LAK cells on tumor cell clonogenicity in soft agar was also enhanced by both bsAb. These results indicate that application of the therapy with LAK cells and OKT3 x LU246 bsAb to SCLC patients might be a promising new method of adoptive immunotherapy.