Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells

Mol Ther. 2014 May;22(5):1029-38. doi: 10.1038/mt.2014.28. Epub 2014 Feb 27.

Abstract

Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy, Adoptive
  • Mice
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Xenograft Model Antitumor Assays

Substances

  • Receptors, Antigen, T-Cell
  • Receptor, ErbB-2