title: Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients.
abstract: OBJECTIVE
  The aim of the study is to explore the safety of cytotoxic T lymphocytes (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno-associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients.
  
  
  METHODS
  A total of 27 cancer patients with tumor tissue expression positivity and/or sera-elevated level of CEA were subsequently divided into cohort A and B resulted from the ex vivo expansion number of CTLs generated from co-culture of specific transfected DCs with autologous T lymphocytes. Based on the variations of infused number of specific CTL derived from different yields of individualized patients who had experienced various anti-cancer treatments, we compared the patients of low number of CTL cells (2-8 × 10(8) infused, cohort A, 6 cases) with those of higher number (above 8 × 10(8) infused, cohort B, 21 cases) to testify the possible adverse reactions caused by amount of infused CTLs. This study resembled a phase I study aiming for setting up clinical trial of adoptive cellular therapy that conceptually comes from conventional cytotoxic drugs.
  
  
  RESULTS
  The results showed that one case from the each cohort had experienced moderate fever, and four cases with fatigue were seen in cohort B. The symptoms were transient without serious adverse events. For the consideration of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9 stable disease (40 %, 10/25) were observed in 25 patients eligible for evaluation. Sera levels of CEA assay were lowered in six patients. During a median follow-up of 8.1 months, we could not observe severe or chronic adverse reactions related to rAAV-DC infusions. Meanwhile, the variation of number of CTLs infused in this setting did not alter the status of peripheral lymphocyte population.
  
  
  CONCLUSIONS
  These preliminary data suggest that the rAAV-DC immunotherapy is well-tolerated and showed no severe adverse reactions in cancer patients.
authors.affiliation: Department of Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), Peking University School of Oncology/Beijing Cancer Hospital and Institute, 52 Fucheng Rd, Beijing, 100142, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Di
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Gonghong
authors.initials: G
authors.lastname: Song
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Che
authors.forename: Huabing
authors.initials: H
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Chunrong
authors.initials: C
authors.lastname: Zhang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Yuan
authors.forename: Miaoning
authors.initials: M
authors.lastname: You
authors.forename: Fengling
authors.initials: F
authors.lastname: Wan
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D014162:Transfection
chemical_list: D019496:Cancer Vaccines