Effects of Platinum Antitumor Agents on in vitro Assays of Human Antitumor Immunity

Abstract

Human lymphoblast cell lines (LCL) [CCRF-CEM, CCRF-HSB-2, CCRF-SB and RPMI 7666 cells] were treated with the antitumor complex cis-[Pt(NH3)2Cl2] (CPDC). Direct effects of CPDC treatment on LCL growth and on LCL recognition by human lymphocytes in vitro are reported. Treatment of LCL with 10 .mu.M CPDC strongly inhibits DNA and protein synthesis, but has little effect on LCL viability. At this concentration, CPDC also inhibits the proliferation of human peripheral blood lymphocytes (PBL) in response to mitogens or allogeneic cells. Therefore, studies of LCL recognition by human PBL were conducted using CPDC pretreated and extensively washed LCL. Recognition of CPDC pretreated LCL in the in vitro mixed lymphocyte tumor (MLT) cell assay for the activation phase of cellular immunity is reduced. The decrease in MLT response is not due to direct effects of the complex on the responding T [thymus derived] lymphocytes, but may be due to lowered antigen expression of treated LCL or other mechanisms. If CPDC does enhance tumor rejection in vivo, it does not appear to be due to enhanced recognition by T cells.