Follicle-Stimulating hormone receptor as a target in the redirected T-cell therapy for cancer

Katarzyna Urbanska, Caitlin Stashwick, Mathilde Poussin, Daniel J. Powell

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Adoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell-based immunotherapy targeting human folliclestimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-Associated vasculature. Receptor ligand-based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHRtargeted immune therapy approaches for patients with cancer.

Original languageEnglish (US)
Pages (from-to)1130-1137
Number of pages8
JournalCancer Immunology Research
Volume3
Issue number10
DOIs
StatePublished - Oct 2015

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

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