Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4

Cell. 1992 Dec 24;71(7):1093-102. doi: 10.1016/s0092-8674(05)80059-5.

Abstract

Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+B7- tumors at distant sites and was curative for established E7+B7- micrometastases. Our findings suggest that increasing T cell costimulation through the CD28 and CTLA-4 receptors may have therapeutic usefulness for generating immunity against tumors expressing viral antigens.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD / immunology*
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, Surface / immunology*
  • Antigens, Viral / immunology
  • CD28 Antigens
  • CTLA-4 Antigen
  • Cell Line
  • Female
  • Immunoconjugates*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Regression, Spontaneous / immunology*
  • Neoplasms, Experimental / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • Antigens, Viral
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Abatacept