title: Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: findings from a pilot study.
abstract: BACKGROUND
  Dendritic cell (DC)-based and cytokine-induced killer cell (CIK)-based therapy can induce specific antitumor T-cell responses. This clinical pilot study examined the safety, the feasibility, and the outcome of tumor-specific immunotherapy for patients with advanced pancreatic adenocarcinoma.
  
  
  METHODS
  Alpha-Gal epitopes were synthesised on pancreatic carcinoma cell membranes with α1,3-galactosyltransferase in vitro. Subsequently, the addition of natural human anti-Gal IgG to the processed membranes resulted in opsonization and effective phagocytosis by DCs, which were co-cultured with newly differentiated CIKs from bone marrow stem cells to generate tumor-specific immune responders ex vivo. Fourteen patients with inoperable stage III/IV pancreatic adenocarcinoma were enrolled in the study; the treatment procedure consisted of injections of DCs and CIKs.
  
  
  RESULTS
  Clinical observation showed that the procedure was safe and lacked serious side effects. Tests showed that 12 patients had strong positive delayed-type IV hypersensitivity to the autologous cancer cell lysate; robust systemic cytotoxicity elicited by interferon (IFN)γ expression by peripheral blood mononuclear cells; and significant increases in CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells in peripheral blood lymphocytes after 3 injections. During the follow up, the percentages of CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells returned to the normal range at 6 to 9 months after the third injection and IFNγ expression in the cells stayed at the higher level from the third injection to 24 months after the treatment.
  
  
  CONCLUSIONS
  This new tumor-specific immunotherapy is safe, feasible, and has great potential for pancreatic carcinoma treatment.
authors: Department of Oncology, First Teaching Hospital, Inner Mongolia Medical College, Huhhot, China.
authors: Ying
authors: Y
authors: Qiu
authors: Mark M
authors: MM
authors: Yun
authors: Ming Bao
authors: MB
authors: Xu
authors: Yi Zhong
authors: YZ
authors: Wang
authors: Sheng
authors: S
authors: Yun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation / Q000379:methods; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D016896:Treatment Outcome; D014312:Trisaccharides / Q000138:chemical synthesis / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens