Interferon-γ-induted intercellular adhesion molecule-1: Expression on human tumor cells enhances bifunctional antibody-mediated lysis through a lymphocyte function-associated antigen-1 dependent mechanism

Patrick S. Ramsey, Phillip A. Dean, Aliza Tasimowicz-Alpini, John H. Donohue, Heidi Nelson

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Abstract

Antitumor x anti-CD3 bifunctional antibodies (BFAs) affect tumor cell lysis by activating and physically linking T-cells and tumor cells. Since tumor target antigen expression does not correlate with susceptibility to BFA-mediated tumor cytotoxicity, we investigated the role of cell adhesion molecules as accessory molecules. In 3 human colon tumor cell lines (LS174T, WIDR, and COLO205), recombinant interferon-γ (rIFN-γ) consistently increased BFA-mediated tumor cell lysis by cultured peripheral blood lymphocytes and consistently increased tumor cell expression of intercellular adhesion molecule-1 (ICAM-1). Using cell conjugation assays, we demonstrated that ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) interactions were important for effector-to-target cell conjugate formation and demonstrated that tumor cell pretreatment with rIFN-γ enhanced cell conjugate formation. Whereas anti-LFA-1 blocked all BFA-mediated tumor lysis and conjugate formation, anti-ICAM-1 blocked only the enhancing effects of rIFN-γ for both cytolysis and conjugate formation. Although BFAs were shown to provide effector-to-target cell bridging, LFA-1 was found to be a common critical element required for BFA-mediated cell conjugation and lysis. ICAM-1, which was augmented by rIFN-γ, appears to be only one of several ligands interacting with LFA-1. These results provide one explanation as to why high expression of tumor-associated antigen alone does not predict the susceptibility to BFA-mediated lysis and provides further support for the concept of combined modality immune therapies.

Original languageEnglish (US)
Pages (from-to)4652-4657
Number of pages6
JournalCancer Research
Volume53
Issue number19
StatePublished - Oct 1 1993

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Bispecific Antibodies
Lymphocyte Function-Associated Antigen-1
Intercellular Adhesion Molecule-1
Interferons
Neoplasms
Neoplasm Antigens
Cultured Tumor Cells
Combined Modality Therapy
Cell Adhesion Molecules
Tumor Cell Line
Colon
Lymphocytes
Ligands
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interferon-γ-induted intercellular adhesion molecule-1 : Expression on human tumor cells enhances bifunctional antibody-mediated lysis through a lymphocyte function-associated antigen-1 dependent mechanism. / Ramsey, Patrick S.; Dean, Phillip A.; Tasimowicz-Alpini, Aliza; Donohue, John H.; Nelson, Heidi.

In: Cancer Research, Vol. 53, No. 19, 01.10.1993, p. 4652-4657.

Research output: Contribution to journalArticle

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