Chimeric scFv/γ receptor-mediated T-cell lysis of tumor cells is coregulated by adhesion and accessory molecules

作者：M. E. M. Weijtens, Ralph A. Willemsen, B.A. Van Krimpen, R. L. H. Bolhuis · 发表于：International Journal of Cancer · 年份：1998 · DOI：10.1002/(sici)1097-0215(19980717)77:2<181::aid-ijc2>3.0.co;2-m · 被引用次数：45 · 研究领域：CAR-T cell therapy research、Monoclonal and Polyclonal Antibodies Research、Immune Cell Function and Interaction

Adhesion and accessory molecules play a critical role in T-cell activation and effector function in general and in tumor cell recognition and lysis in particular. We investigated the contribution of CD2, CD3, CD11a/CD18, CD54 and CD58 molecules in T lymphocyte-tumor cell interactions mediated by chimeric immunoglobulin receptors. The chimeric receptor is composed of a single chain antibody binding site and a gamma-chain signal transducing molecule (scFv/gamma). T lymphocytes expressing such scFv/gamma receptors recognize the G250 Ag on renal cell carcinoma (RCC) in an major histocompatibility complex (MHC)-unrestricted manner and exert RCC selective cytolysis. A coregulatory role for CD2, CD3 and CD11a/CD18 molecules in scFv/gamma-mediated cytolysis was demonstrated using monoclonal antibody (MAb)-induced inhibition of scFv/gamma-mediated cytolysis. The inhibition of lysis was not due to inhibition of cytotoxic T lymphocyte (CTL)-target cell conjugation but rather to a post-conjugate signaling event. Binding of CD54 and CD58 MAbs to the RCC did not inhibit cytolysis of RCC cells that expressed high levels of both CD54 and the G250 antigen (Ag) (A75), whereas cytolysis of RCC expressing intermediate levels of CD54 and G250 Ag (SK-RC-17 cl.4) was partly inhibited by the CD54 MAb. Binding of low concentrations of G250 MAb to RCC (A75) rendered these cells sensitive to CD54 MAb inhibition, demonstrating a direct functional relation between G250 Ag expression level and adhesion mo...