title: Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer.
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 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.
authors.affiliation: Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Urbanska
authors.affiliation: Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Stashwick
authors.affiliation: Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Poussin
authors.affiliation: Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. poda@mail.med.upenn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Powell
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011962:Receptors, FSH / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D011962:Receptors, FSH; D011993:Recombinant Fusion Proteins