Cellular Therapy for Ovarian Cancer: Experimental and Clinical Perspectives

    Authors

    S. B. Ingersoll; S. Ahmad; J. F. Neil; J. R. Edwards;R. W. Holloway

    Comments

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    Abbreviated Journal Title

    Curr. Med. Chem.

    Keywords

    Ovarian cancer; cellular therapy; immunosuppression; targeted therapy; experimental models; clinical outcomes; HIGH-DOSE CHEMOTHERAPY; MYELOID SUPPRESSOR-CELLS; NATURAL-KILLER-CELLS; T-REGULATORY-CELLS; BREAST-CANCER; SOLID TUMORS; STAGE-III; INTRAPERITONEAL CISPLATIN; TGF-BETA; NK-CELL; Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &; Pharmacy

    Abstract

    Ovarian cancer is the leading cause of death among gynecologic malignancies and the 5th leading cause of cancer deaths for women in the United States. Two-thirds of patients present with advanced-stage disease (Stage III and IV) and the majority will suffer recurrence of disease, require ongoing treatment, and eventually succumb to chemotherapy-resistant disease. To potentially circumvent chemo-resistance in recurrent ovarian cancer, immunotherapy is being explored as a novel treatment option. Our laboratory findings demonstrate that immune effector cells from healthy donors elicit a significant cytotoxic response in the presence of IL-2 and IFN alpha-2b against ovarian cancer in vitro; however, peripheral blood mononuclear cells (PBMC) isolated from ovarian cancer patients fail to elicit a similar response. A major obstacle to immunotherapy is the immunosuppressive environment supported by tumors, which limits the immune system's ability to fight the tumor. Myeloid-derived suppressor cells are an immature population of myeloid cells, which have recently been implicated to play a major role in immunosuppression and tumor evasion. In addition to novel immunotherapies, new diagnostic and prognostic markers are being identified through applying molecular tools/approaches in clinical and pathological analyses of this malignancy, which will provide additional therapeutic targets. To test these experimental therapeutic options, pre-clinical murine models of ovarian cancer are being developed. Ultimately, treatment of ovarian cancer will benefit from the careful alignment of appropriate target, drug, patient, and trial design. This article provides an objective overview of cellular therapy (the use of immune cells to elicit an anti-tumor response) for ovarian cancer highlighting both experimental and clinical perspectives.

    Journal Title

    Current Medicinal Chemistry

    Volume

    19

    Issue/Number

    22

    Publication Date

    1-1-2012

    Document Type

    Review

    Language

    English

    First Page

    3787

    Last Page

    3793

    WOS Identifier

    WOS:000306494500014

    ISSN

    0929-8673

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