T cells targeted against a single minor histocompatibility antigen can cure solid tumors

Nat Med. 2005 Nov;11(11):1222-9. doi: 10.1038/nm1311. Epub 2005 Oct 16.

Abstract

T cells responsive to minor histocompatibility (H) antigens are extremely effective in curing leukemia but it remains unknown whether they can eradicate solid tumors. We report that injection of CD8(+) T cells primed against the immunodominant H7(a) minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)-gamma-producing H7(a)-specific T cells. Intratumoral release of IFN-gamma had two crucial effects: inhibition of tumor angiogenesis and upregulation of major histocompatibility complex (MHC) class I expression on tumor cells. Despite ubiquitous expression of H7(a), dissemination of a few H7(a)-specific T cells in extralymphoid organs caused neither graft-versus-host disease (GVHD) nor vitiligo because host nonhematopoietic cells were protected by their low expression of MHC class I. Our preclinical model yields unique insights into how minor H antigen-based immunotherapy could be used to treat human solid tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic / genetics
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Immunotherapy*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Congenic
  • Minor Histocompatibility Antigens / immunology*
  • Neoplasm Transplantation
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Neoplasms, Experimental / therapy*
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous

Substances

  • Minor Histocompatibility Antigens
  • Interferon-gamma