Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysis in Vitro and prevent tumor growth in Vivo

Heidi Nelson, Patrick S. Ramsey, David J. McKean, Roger R. Dozois, John H. Donohue

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 × 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 × 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 × 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 × anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalDiseases of the Colon & Rectum
Volume34
Issue number2
DOIs
StatePublished - Feb 1 1991

Keywords

  • Anti-CD3 antibody
  • Colon tumor
  • Cytolysis
  • Heteroconjugates

ASJC Scopus subject areas

  • Gastroenterology

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