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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)
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
October 1992,
International journal of immunopharmacology,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
July 1987,
Proceedings of the National Academy of Sciences of the United States of America,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
June 1991,
Cellular immunology,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
August 1995,
Journal of immunology (Baltimore, Md. : 1950),
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
April 1994,
Cancer immunology, immunotherapy : CII,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
April 1987,
Proceedings of the National Academy of Sciences of the United States of America,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
March 1989,
International journal of cancer,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
March 2001,
Gene therapy,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
November 2000,
Transplantation proceedings,
H Nelson, and
D J McKean, and
L A Kerr, and
J H Donohue
July 1999,
Journal of immunology (Baltimore, Md. : 1950),
