AN IMMUNOCONJUGATE OF LYS(3)-BOMBESIN AND MONOCLONAL-ANTIBODY-22 CAN SPECIFICALLY INDUCE FC-GAMMA-RI (CD64)-DEPENDENT MONOCYTE-MEDIATED ANDNEUTROPHIL-MEDIATED LYSIS OF SMALL-CELL CARCINOMA OF THE LUNG-CELLS

Small cell carcinoma of the lung (SCCL) accounts for 25% of all lung c ancers and has a very poor prognosis. It is known that SCCL cells prod uce gastrin-releasing peptide, a peptide which has similar biological actions to that of bombesin, an amphibian counterpart of gastrin-relea sing peptide, and express high affinity cell surface bombesin/gastrin- releasing peptide receptors. These receptors can serve as targets for specific immunotherapy. Cell surface receptors for the Fc portion of I gG (Fc gamma R) are a family of molecules that can mediate a variety o f immune reactions, including tumor cell cytotoxicity. We hypothesized that an immunoconjugate of bombesin and a mAb directed to the high-af finity Fc gamma RI (mAb 22) should be able to trigger specific cytotox icity against SCCL cells. In this article, we report the construction of this immunoconjugate and demonstrate its capacity to redirect immun e effector cells toward SCCL cells and elicit lysis of these target ce lls. The immunoconjugate stained the majority of cells from four SCCL cell lines and reacted with Fc gamma RI on activated monocytes and neu trophils. After preincubating monocytes and neutrophils with recombina nt gamma interferon to enhance the expression of Fc gamma RI on the ce ll surface, we demonstrated that 60-98% of SCCL cells could be lysed i n the presence of the immuno-conjugate in a chromium release assay. Tu mor cell lysis was observed over a wide range of immunoconjugate conce ntrations, was dependent on the ratio of E:T cells, and could be block ed by the addition of either parental molecule of the immunoconjugate. Bispecific molecules redirecting immune effector cells to target SCCL cells may have clinical application in the therapy of SCCL.