Comparison of the cytotoxic response against ovarian cancer by immune effector cells isolated and expanded from normal donors and ovarian cancer patients

    Authors

    S. B. Ingersoll; G. P. Stoltzfus; M. H. Merchant; S. Ahmad; C. R. Edwards; A. Ahmed; J. L. Oyer; N. J. Finkler; R. W. Holloway;J. R. Edwards

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    Abbreviated Journal Title

    Cytotherapy

    Keywords

    cell expansion; cytokines; cytotoxicity; ovarian cancer; T cells; T-CELLS; SUPPRESSOR-CELLS; CELLULAR THERAPY; CYTO-TOXICITY; TGF-BETA; NK-CELL; TUMOR; CYCLOPHOSPHAMIDE; RECOGNITION; COMBINATION; Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell; Biology; Hematology; Medicine, Research & Experimental

    Abstract

    Background/Aims. The aim of this study was to compare the cytotoxic response against ovarian cancer (OC) cells elicited by different immune effector cells in combination with the cytokines interleukin (IL)-2 and interferon (IFN) alpha-2b. Methods. OC cells were co-cultured with peripheral blood mononuclear cells (PBMC) from normal donors or OC patients and IL-2 or IFN alpha-2b alone or in combination, in order to determine the cytotoxicity. T cells were isolated from healthy donors to determine T cell cytotoxic activity. PBMC from healthy donors and OC patients were expanded in an IL-2/IL-7/IL-12 cocktail with and without anti-CD3 antibody, and the cytotoxic activity measured. Flow cytometry was performed on primary, selected and expanded cells to determine T, B, and natural killer-(NK) cell percentages. Results. Healthy donor PBMC elicited a significant cytotoxic response (59%) compared with OC patient PBMC (7%). T cells enriched from normal donors elicited a significant cytotoxic response (18%) compared with controls lacking effector cells (1.4%); however, the cytotoxicity observed was significantly less compared with unselected PBMC. Expanded effector cells consisted primarily of T cells (98%) and the fold-expansion was significantly higher in the presence of anti-CD3 (19-versus 132-fold). No significant difference in the expansion (either fold-expansion or cell type) was observed between OC patients and healthy donors. Expanded cells from both healthy donors and OC patients elicited a significant cytotoxic response in the presence of IL-2 (19% and 22%) compared with controls. Conclusions. PBMC from OC patients do not elicit a significant cytotoxic response; however, ex vivo-expanded cells from OC patients are capable of cytotoxic killing similar to unexpanded T cells isolated from normal donors. These data provide the groundwork for further development of cellular therapy against OC.

    Journal Title

    Cytotherapy

    Volume

    14

    Issue/Number

    6

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    716

    Last Page

    723

    WOS Identifier

    WOS:000305115100010

    ISSN

    1465-3249

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