RT Journal Article
SR Electronic
T1 Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 1130
OP 1137
DO 10.1158/2326-6066.CIR-15-0047
VO 3
IS 10
A1 Urbanska, Katarzyna
A1 Stashwick, Caitlin
A1 Poussin, Mathilde
A1 Powell, Daniel J.
YR 2015
UL http://cancerimmunolres.aacrjournals.org/content/3/10/1130.abstract
AB 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 follicle-stimulating 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 FSHR-targeted immune therapy approaches for patients with cancer. Cancer Immunol Res; 3(10); 1130–7. ©2015 AACR.