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 Citations (Scopus)

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 demonstratedin 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′)2heteroconjugates 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 1991

Fingerprint

Colon
Lymphocytes
Growth
Neoplasms
Neoplasm Antibodies
Anti-Idiotypic Antibodies
Colonic Neoplasms
T-Cell Antigen Receptor-CD3 Complex
In Vitro Techniques
T-Lymphocytes
Surface Antigens
Nude Mice
Immunotherapy
Monoclonal Antibodies

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysis in Vitro and prevent tumor growth in Vivo. / Nelson, Heidi; Ramsey, Patrick S.; McKean, David J.; Dozois, Roger R.; Donohue, John H.

In: Diseases of the Colon & Rectum, Vol. 34, No. 2, 02.1991, p. 140-147.

Research output: Contribution to journalArticle

Nelson, Heidi ; Ramsey, Patrick S. ; McKean, David J. ; Dozois, Roger R. ; Donohue, John H. / Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysis in Vitro and prevent tumor growth in Vivo. In: Diseases of the Colon & Rectum. 1991 ; Vol. 34, No. 2. pp. 140-147.
@article{c8e225a1674b4678b8a347557b45a6f0,
title = "Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysis in Vitro and prevent tumor growth in Vivo",
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 demonstratedin 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′)2heteroconjugates 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.",
keywords = "Anti-CD3 antibody, Colon tumor, Cytolysis, Heteroconjugates",
author = "Heidi Nelson and Ramsey, {Patrick S.} and McKean, {David J.} and Dozois, {Roger R.} and Donohue, {John H.}",
year = "1991",
month = "2",
doi = "10.1007/BF02049988",
language = "English (US)",
volume = "34",
pages = "140--147",
journal = "Diseases of the Colon and Rectum",
issn = "0012-3706",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysis in Vitro and prevent tumor growth in Vivo

AU - Nelson, Heidi

AU - Ramsey, Patrick S.

AU - McKean, David J.

AU - Dozois, Roger R.

AU - Donohue, John H.

PY - 1991/2

Y1 - 1991/2

N2 - 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 demonstratedin 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′)2heteroconjugates 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.

AB - 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 demonstratedin 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′)2heteroconjugates 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.

KW - Anti-CD3 antibody

KW - Colon tumor

KW - Cytolysis

KW - Heteroconjugates

UR - http://www.scopus.com/inward/record.url?scp=0026011781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026011781&partnerID=8YFLogxK

U2 - 10.1007/BF02049988

DO - 10.1007/BF02049988

M3 - Article

C2 - 1825192

AN - SCOPUS:0026011781

VL - 34

SP - 140

EP - 147

JO - Diseases of the Colon and Rectum

JF - Diseases of the Colon and Rectum

SN - 0012-3706

IS - 2

ER -