title: Combination of cytokine-induced killer and dendritic cells pulsed with antigenic α-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy.
abstract: OBJECTIVE
  Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients.
  
  
  METHODS
  Fourteen refractory lymphoma patients (age, 29-74 y) were enrolled in the trial. α-1,3-galactosyl (α-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant α-1,3-galactosyltransferase (α-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti-α-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine-induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donor lymphoma patients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment.
  
  
  RESULTS
  Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and β2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment.
  
  
  CONCLUSIONS
  Lymphoma cell-specific α-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Heart of England National Health Service Foundation Trust, Bordesley Green, East Birmingham, UK.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Yun
authors.affiliation: Guy's and St Thomas' Hospital National Health Service Foundation Trust, London, UK.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Beijing Armed Police General Hospital, Beijing, China.
authors.forename: Mingbao
authors.initials: M
authors.lastname: Xu
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Han
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Zhou
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Feiyu
authors.initials: F
authors.lastname: Yun
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Wuyun
authors.initials: W
authors.lastname: Su
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Second Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tong
authors.affiliation: Jing-Meng Stem Cell Company, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ouyang
authors.affiliation: Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. Electronic address: sheng.yun@hotmail.co.uk.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yun
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005690:Galactose / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D007371:Interferon-gamma; D005690:Galactose
keywords: cytokine-induced killer; dendritic cell; epitope; immunotherapy; refractory lymphoma; α-1,3-galactosyl epitope