title: T-cell target antigens across major gynecologic cancers.
abstract: Immunotherapies have achieved remarkable success in treating different forms of cancer including melanoma, non-small cell lung carcinoma, bladder cancer, synovial cell sarcoma, and multiple myeloma using immune checkpoint blockade or gene-engineered T-cells. Although gynecologic cancers have not been historically classified as immunogenic tumors, growing evidence has shown that they are in fact able to elicit endogenous antitumor immune responses suggesting that patients with these cancers may benefit from immunotherapy. Modest clinical success has been accomplished in early trials using immunotherapeutic modalities for major gynecologic cancers including ovarian, cervical, and endometrial cancer. Unlike solid cancers with high mutational burdens, or hematologic malignancies where target antigens are expressed homogenously and exclusively by tumor cells, identifying tumor-restricted antigens has been challenging when designing a T-cell targeted therapy for gynecologic tumors. Nevertheless, mounting preclinical and clinical evidence suggests that targeting shared, viral or patient-specific mutated antigens expressed by gynecologic tumors with T-cells may improve patient outcome. Here we review the strengths and weaknesses of targeting these various antigens, as well as provide insight into the future of immunotherapy for gynecologic cancers.
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Alba
authors.initials: A
authors.lastname: Rodriguez-Garcia
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Minutolo
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Gynecologic Oncology, MD Anderson Cooper Cancer Center, Cooper University Hospital, Camden, NJ 08103, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Robinson
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: poda@mail.med.upenn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Powell
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D005833:Genital Neoplasms, Female / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D058990:Molecular Targeted Therapy; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines
keywords: Cancer antigen; Cervical cancer; Chimeric antigen receptor; Endometrial cancer; Immunotherapy; Ovarian cancer; T-cell receptor