ANTI-TUMORXANTI-LYMPHOCYTE HETEROCONJUGATES AUGMENT COLON-TUMOR CELL-LYSIS INVITRO AND PREVENT TUMOR-GROWTH INVIVO

Cross-linking an anti-tumor antibody, specific for tumor cell surface antigens, and an anti-lymphocyte antibody, specific for the T lymphocyte receptor complex (TCR/CD3), produces a heteroconjugate that can direct T cells to lyse tumor cells. We tested the ability of anti-tumor x anti-lymphocyte (CD3) heteroconjugates to redirect human peripheral blood lymphocytes (PBLs) to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model. We demonstrated in vitro, that cultured human PBLs alone produced low levels of tumor lysis, but PBLs treated with anti-tumor x anti-CD3 heteroconjugates produced significantly greater tumor cell lysis (P < 0.0025). Similarly, nude mice injected with LS174T human colon cancer cells and treated with cultured human PBLs and anti-tumor x anti-CD3 heteroconjugates survived significantly longer than saline control mice (P < 0.01), or mice treated with PBLs alone (P < 0.01), or heteroconjugates alone (P < 0.05). F(ab')2 heteroconjugates were equally as effective in prolonging animal survival, but irrelevant heteroconjugates and monoclonal anti-tumor antibodies showed no therapeutic benefit. Anti-tumor x anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy.