Anti-tumor x anti-CD3 heteroconjugates direct human peripheral blood lymphocytes to lyse colon tumor cells.
T lymphocytes normally recognize antigens through the antigen receptor complex (TCR/CD3) but can be redirected to bind and lyse unrecognized tumor cells by anti-tumor X anti-CD3 heteroconjugates. Chemical coupling of an antibody directed against the T cell receptor complex and an antibody directed against tumor antigen produces a conjugated antibody that activates the T cell lytic mechanism and bridges the T cell and tumor cell. We tested the lytic activity of heteroconjugate-treated cultured human peripheral blood lymphocytes (PBLs) in 4-h radioactive chromium release assays with human colon tumor cell targets. PBLs were enriched for T cells by the depletion of Leu11a+ and Leu19+ cells, prior to culture in rIL-2 and anti-CD3. Cultured human PBLs depleted of Leu11a+ and Leu19+ cells produced low levels of tumor cell lysis in the absence of antibodies. Anti-tumor X anti-CD3 heteroconjugates significantly enhanced tumor cell lysis by cultured PBLs when tested against four different colon tumor cell lines (P less than 0.005), but, heteroconjugates in the absence of PBLs did not augment tumor cell lysis. Cultured PBLs treated with monoclonal anti-tumor antibody, with monoclonal anti-CD3 antibody, or with irrelevant heteroconjugate did not enhance tumor cell lysis. We conclude that heteroconjugate-directed lysis is mediated by PBLs and that both the anti-tumor antibody and the anti-CD3 antibody are essential for heteroconjugate function. In addition, heteroconjugate-enhanced tumor cell lysis is mediated through a mechanism other than antibody-dependent cellular cytotoxicity or nonspecific T cell receptor crosslinking.(ABSTRACT TRUNCATED AT 250 WORDS)
Nelson
H
H
Department of Surgery, Mayo Foundation, Rochester, Minnesota 55905.
McKean
D J
DJ
Kerr
L A
LA
Donohue
J H
JH
D000906:Antibodies / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D001696:Biomechanical Phenomena; D001773:Blood Cells / Q000166:cytology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000912:Antibodies, Neoplasm; D015703:Antigens, CD