title: Comparison of the cytotoxic response against ovarian cancer by immune effector cells isolated and expanded from normal donors and ovarian cancer patients.
abstract: OBJECTIVE
  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) α-2b.
  
  
  METHODS
  OC cells were co-cultured with peripheral blood mononuclear cells (PBMC) from normal donors or OC patients and IL-2 or IFN α-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.
authors.affiliation: Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, Florida 32804, USA. susan.blaydes@fl hosp.org
authors.forename: Susan Blaydes
authors.initials: SB
authors.lastname: Ingersoll
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Stoltzfus
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Merchant
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Collin R
authors.initials: CR
authors.lastname: Edwards
authors.forename: Ahad
authors.initials: A
authors.lastname: Ahmed
authors.forename: Jeremiah L
authors.initials: JL
authors.lastname: Oyer
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Finkler
authors.forename: Robert W
authors.initials: RW
authors.lastname: Holloway
authors.forename: John R
authors.initials: JR
authors.lastname: Edwards
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006262:Health; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins