Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine Anti-p53 TCR

Cyrille J. Cohen, Zhili Zheng, Regina Bray, Yangbing Zhao, Linda A. Sherman, Steven A. Rosenberg, Richard A. Morgan

Research output: Contribution to journalArticle

Abstract

The p53 protein is markedly up-regulated in a high proportion of human malignancies. Using an HLA-A2 transgenic mouse model, it was possible to isolate high-avidity murine CTLs that recognize class I-restricted human p53 epitopes. We isolated the α- and β-chain of a TCR from a highly avid murine CTL clone that recognized the human p53264-272 epitope. These genes were cloned into a retroviral vector that mediated high efficiency gene transfer into primary human lymphocytes. Efficiencies of >90% for gene transfer into lymphocytes were obtained without selection for transduced cells. The p53 TCR-transduced lymphocytes were able to specifically recognize with high-avidity, peptide-pulsed APCs as well as HLA-A2.1+ cells transfected with either wild-type or mutant p53 protein. p53 TCR-transduced cells demonstrated recognition and killing of a broad spectrum of human tumor cell lines as well as recognition of fresh human tumor cells. Interestingly, both CD8+ and CD4+ subsets were capable of recognizing and killing target cells, stressing the potential application of such a CD8-independent TCR molecule that can mediate both helper and cytotoxic responses. These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies.

Original languageEnglish (US)
Pages (from-to)5799-5808
Number of pages10
JournalJournal of Immunology
Volume175
Issue number9
DOIs
StatePublished - Nov 1 2005

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this