MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo

Pinku Mukherjee, Amelia R. Ginardi, Teresa L. Tinder, Christopher J. Sterner, Sandra J. Gendler

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

We have reported previously that MUC1 transgenic mice with spontaneous tumors of the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1-specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451-3460, 2000). From these MET mice, we have isolated, expanded, and cloned naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vβ chains 5.1/5.2, 11, 13, and 2 and Vα chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem repeat with highest affinity to APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a single Vβ chain of 5.1/5.2 and Vα2. It recognizes only the H-2Db class I-restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were effective in eradicating MUC1-expressing injected tumor cells including mammary gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation. To our knowledge, this is the first evidence that demonstrates that the naturally occurring MUC1-specific CTLs isolated from one tumor model has antitumor effects on other MUC1-expressing tumors in vivo. Therefore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.

Original languageEnglish (US)
Pages (from-to)848s-855s
JournalClinical Cancer Research
Volume7
Issue number11 SUPPL.
StatePublished - Mar 1 2001

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mukherjee, P., Ginardi, A. R., Tinder, T. L., Sterner, C. J., & Gendler, S. J. (2001). MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo. Clinical Cancer Research, 7(11 SUPPL.), 848s-855s.