Combination therapy of the H2712 murine mammary carcinoma with cytotoxic T lymphocytes and anti-estrogens

Anticancer Res. Sep-Oct 1997;17(5A):3647-51.

Abstract

Background: The triphenylethylene antiestrogenic agents, tamoxifen (TX) and toremifene (TO), are currently being used for the therapy of estrogen dependent breast carcinomas and for some other estrogen receptor positive tumors. Some observations indicate that these drugs may have a beneficial effect on estrogen receptor negative tumors as well.

Materials and methods: The H2712 mammary carcinoma of C3H/HeJ mice was studied in combination immunotherapy experiments using cytotoxic T lymphocytes (CTL) and TX or TO. The effect of TX and TO on the in vitro lysis of H2712 cells by CTL was also investigated. Finally, the H2712 cells were examined for the presence of estrogen receptors.

Results: Both TX and TO potentiated the lysis of H2712 cells by CTL in vitro, and exerted a growth inhibitory and therapeutic effect on H2712 mammary carcinomas in vivo. The therapeutic effect of CTL isolated from tumor bearing mice was improved on H2712 carcinomas when the animals were also treated orally by TX or TO. Using the dextran-coated charcoal assay, H2712 cells were found to be negative for classical estrogen receptors.

Conclusions: These results indicate that the anti-estrogens, TX and TO, have the ability to suppress the growth of the estrogen receptor negative mammary carcinoma and to amplify target cell lysis by tumor-reactive CTL. By this mechanism these drugs enhance host immunity to an estrogen receptor negative tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Combined Modality Therapy
  • Cytotoxicity, Immunologic
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Immunotherapy
  • Interferon-gamma / therapeutic use
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred C3H
  • Spleen / immunology
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tamoxifen / therapeutic use*
  • Toremifene / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Tamoxifen
  • Toremifene
  • Interferon-gamma