Acquired erythropoietin responsiveness of interleukin-2-dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors

Seijiro Minamoto, Jonathan Treisman, W. David Hankins, Kazuo Sugamura, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, β and γ, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs.

Original languageEnglish (US)
Pages (from-to)2281-2287
Number of pages7
JournalBlood
Volume86
Issue number6
DOIs
StatePublished - Sep 15 1995

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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