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T cell memory against colon carcinoma is long-lived absence of antigen

Academic Article
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Overview

authors

  • Xiang, R.
  • Lode, H. N.
  • Gillies, S. D.
  • Reisfeld, Ralph

publication date

  • October 1999

journal

  • Journal of Immunology  Journal

abstract

  • Eradication of established colon carcinoma metastases is a major goal for adjuvant immunotherapy of this disease. This was accomplished in a murine model by targeting IL-2 to the tumor microenvironment with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2). The generation of a long-lived protective immunity was demonstrated by a 10- to 14-fold increase in CTL precursor (pCTL) frequency and induction of genes encoding Th1 cytokines, followed by the generation of tumor-specific CD8+ T effector cells, some of which differentiated into long-lived T memory cells. The frequency of pCTL correlated with enhanced immune protection against tumor cell challenge, and long-lived T cell memory was maintained in syngeneic SCID mice in the absence of tumor Ag. Tumor cell challenge of these SCID mice, concomitant with a boost of two noncurative doses of huKS1/4-IL-2 fusion protein, resulted in the generation of primed CD8+ T effector cells with concurrent release of Th1 cytokines. These events culminated in the complete rejection of the tumor cell challenge and prevention of pulmonary metastases. Taken together, the data suggest that T cell memory against colon carcinoma can be maintained in the absence of Ag.

subject areas

  • Animals
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes
  • Cell Adhesion Molecules
  • Cell Differentiation
  • Colonic Neoplasms
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunologic Memory
  • Interleukin-2
  • Lymphocyte Activation
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Recombinant Fusion Proteins
  • Stem Cells
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic
  • Th1 Cells
  • Time Factors
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 10490962
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Additional Document Info

start page

  • 3676

end page

  • 3683

volume

  • 163

issue

  • 7

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