ICAM-1 increases in vitro adhesion and cytotoxicity in a murine fibrosarcoma

Cellular adhesion and specific cytotoxicity are two essential components for the successful cellular therapy of cancer. Intercellular adhesion molecule-1 (ICAM-1) is an essential participant in lymphocyte-endothelial cell adhesion and may also play a role in lymphocyte-mediated cytotoxicity. To study the effect of ICAM-1 on adhesion and cytotoxicity in vitro, MCA-105 tumor cells were cotransfected with ICAM-1 and the gene for neomycin resistance (NeoR). Two clones (Clones 81 and 149) with confirmed enhancement of ICAM-1 expression were selected. Studies were performed examining adhesion of lymphocytes to HUVECs, MCA-105, Clone 81 or Clone 149 alone, or combinations of the three tumor cell lines with HUVECs. Peripheral blood lymphocytes labeled with Cr-51 were used and adhesion was determined by counting in a gamma-counter after rinsing away nonadherent cells. Cytotoxicity was performed using Cr-51-labeled MCA-105, NeoR, Clone 81, and Clone 149 target cells. LAK cells cultured from splenocytes of normal mice were used as the effector cells and a chromium release assay was performed. Adhesion data showed significant increases in adhesion (P < 0.05) for Clones 81 and 149 compared to MCA-105. However, the combination of HUVECs and tumor cells to mimic the in vivo condition had a variable effect on adhesion compared to tumor cells alone. Cytotoxicity experiments demonstrated that Clone 149 was significantly (P < 0.05) more susceptible to lysis by normal LAK cells compared to MCA-105, NeoR, and Clone 81. These results suggest that increased ICAM-1 expression enhances the susceptibility of tumor cells to lysis by LAK cells. (C) 1996 Academic Press, Inc.