title: Ovarian malignant ascites-derived lymphocytes stimulated with prothymosin α or its immunoactive decapeptide lyse autologous tumour cells in vitro and retard tumour growth in SCID mice.
abstract: BACKGROUND
  Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells are of clinical importance. The immunomodulator prothymosin alpha (proTα) increases the specific lysis of tumour cells by activated CD8(+) T-lymphocytes and its immunoreactivity is exerted by the carboxy-terminal decapeptide, proTα(100-109). These two molecules were studied on TALs in vitro, and in SCID mice bearing human ovarian tumours.
  
  
  METHODS
  TALs and tumour cells were isolated from 41 ovarian cancer patients and co-cultured in the presence of proTα or proTα(100-109). The cytotoxicity of peptide-stimulated TALs was tested against autologous tumour cells and K562. Ex vivo peptide-stimulated TALs from three patients were adoptively transferred intraperitoneally in SCID mice, previously inoculated with each patient's autologous tumour cells.
  
  
  RESULTS
  ProTα and its immunoreactive peptide proTα(100-109), enhanced the cytotoxic activity of TALs against autologous tumour cells in vitro, but marginally affected the lysis of K562. The effect of proTα and proTα(100-109) was higher after 7-14 days of stimulation, whereas TAL cytotoxicity was significantly decreased after 21 days. Mice administered TALs, ex vivo activated with proTα or proTα(100-109) for 7 days, showed a relatively lower tumour increase rate and a prolongation of their survival, compared to controls.
  
  
  CONCLUSIONS
  Our data demonstrate that, in the presence of tumour antigens, proTα and proTα(100-109) enhance the depressed cytotoxicity of TALs against autologous tumour cells in vitro and retard tumour growth in vivo.
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioannis F
authors.initials: IF
authors.lastname: Voutsas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pistamaltzian
authors.forename: Marinos L
authors.initials: ML
authors.lastname: Tsiatas
authors.forename: Margarita
authors.initials: M
authors.lastname: Skopeliti
authors.forename: Theodora
authors.initials: T
authors.lastname: Katsila
authors.forename: Ilektra
authors.initials: I
authors.lastname: Mavrothalassiti
authors.forename: Spyros
authors.initials: S
authors.lastname: Spyrou
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Ourania E
authors.initials: OE
authors.lastname: Tsitsilonis
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001201:Ascites / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D020014:K562 Cells; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011498:Protein Precursors / Q000737:chemistry / Q000494:pharmacology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D009842:Oligopeptides; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin