Effects of HC antibody in autologous tumor-specific cytotoxicity by human melanoma tumor-infiltrating lymphocytes

✍ Scribed by Paul F. Mansfield; Marie A. Salmeron; Michael G. Rosenblum; Kyogo Itoh

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 689 KB
• Volume: 49
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910490307

✦ Synopsis

Abstract

Heteroconjugate (HC) antibody has a potential use in cancer biotherapy because of its ability to mimic antigenic specificity and induce cytotoxicity in the activated lymphocytes against various tumor cells. This study investigated the effects of HC antibody (anti‐CD3 MAb x anti‐p97 melanoma cell MAb) in autologous tumor‐specific cytotoxicity by interleukin‐2 (IL‐2)‐activated melanoma tumor‐infiltrating lymphocytes (TILs). HC antibody significantly augmented p97^pos^ uncultured autologous tumor cell lysis mediated by effector TILs or cytotoxic T lymphocyte (CTL) clones derived from TIL. It did not significantly increase p97^mix^ autologous tumor‐cell lysis and slightly inhibited the lysis only at higher E:T ratios and higher concentrations (≥ 100 ng/ml). It inhibited p97^neg^ autologous tumor‐cell lysis. HC antibody respectively induced potent lysis of p97^pos^ or modest lysis of p97^mix^ tumor cells by allogeneic effector TILs as well as PBMC. In contrast, parental anti‐CD3 MAb primarily suppressed the autologous tumor‐specific cytotoxicity, and did not induce lysis of uncultured melanoma cells, regardless of differences in expression of p97 antigens on tumor cells. Although parental anti‐p97 MAb did not augment or suppress the autologous tumor‐specific cytotoxicity, it completely abrogated HC antibody‐mediated augmentation of p^97pos^ autologous tumor cell lysis by effector TILs. Anti‐class‐IMAb, but not anti‐DR MAb, suppressed the autologous tumor‐specific cytotoxicity, but failed to block HC antibody‐mediated augmentation of p97^pos^ autologous tumor‐cell lysis. These results suggest that the levels of p97 antigen expression largely influenced HC antibody‐mediated modulation of TIL cytotoxicity against uncultured autologous tumor cells.