Enhancing the specificity of T-cell cultures for adoptive immunotherapy of cancer

Connie Pm Duong, Jennifer A. Westwood, Linda J. Berry, Phillip K. Darcy, Michael H. Kershaw

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

Abstract

Adoptive immunotherapy is a promising approach for the treatment of cancer; however, autoimmunity against normal tissue can be a serious complication of this therapy. We hypothesized that T-cell cultures responding maximally only when engaging two antigens would be more specific for tumor cells, and less active against normal cells, as long as the tumor expressed both antigens, while normal cells expressed only one of the antigens. A model system was developed consisting of cell lines expressing either folate binding protein or erbB-2, representing 'normal tissue, and cells expressing both antigens representing tumor tissue. Human T-cell cultures were produced using two chimeric antigen receptor vectors ('dual transduced), or using a single chimeric antigen receptor vector (monospecific). Dual-transduced T cells responded less against 'normal cells compared with tumor cells. This relatively simple procedure produced T-cell cultures that were as active against a tumor as the monospecific cultures used traditionally, but had lower activity against model normal cells.

Original languageEnglish
Pages (from-to)33-48
Number of pages16
JournalImmunotherapy
Volume3
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

  • breast cancer
  • cancer
  • chimeric antigen receptor
  • gene therapy
  • sarcoma
  • tumor immunology

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