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: Katarzyna Urbanska, Caitlin Stashwick, Mathilde Poussin, Daniel J Powell Jr
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 3 Issue 10 Pg. 1130-7 (Oct 2015) ISSN: 2326-6074 [Electronic] United States
• PMID: 26112923 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antigens, Neoplasm
• Receptors, FSH
• Recombinant Fusion Proteins

Topics

• Animals
• Antigens, Neoplasm (genetics, immunology)
• Cell Line
• Cytotoxicity, Immunologic
• Disease Models, Animal
• Female
• Gene Expression
• Gene Order
• Genetic Vectors (genetics)
• Humans
• Immunotherapy, Adoptive (methods)
• Mice
• Neoplasms (genetics, immunology, therapy)
• Ovarian Neoplasms (genetics, immunology, pathology, therapy)
• Receptors, FSH (genetics, immunology)
• Recombinant Fusion Proteins (genetics, immunology)
• T-Cell Antigen Receptor Specificity (immunology)
• T-Lymphocytes (immunology, metabolism)
• Tumor Burden
• Xenograft Model Antitumor Assays