title: Comparison of two CD40-ligand/interleukin-2 vaccines in patients with chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Several studies have demonstrated that the immunogenicity of chronic lymphocytic leukemia (CLL) cells can be increased by manipulation of the CD40/CD40-ligand (CD40L) pathway. Although immunologic, and perhaps clinical, benefits have been obtained with an autologous CLL tumor vaccine obtained by transgenic expression of CD40L and interleukin (IL)-2, there is little information about the optimal gene transfer strategies.
  
  
  METHODS
  We compared two different CLL vaccines prepared by adenoviral gene transfer and plasmid electroporation, analyzing their phenotype and immunostimulatory activity.
  
  
  RESULTS
  We found that higher expression of transgenic CD40L was mediated by adenoviral gene transfer than by plasmid transduction, and that adenoviral transfer of CD40L was associated with up-regulation of the co-stimulatory molecules CD80 and CD86 and adhesion molecule CD54. In contrast, transgenic IL-2 secretion was greater following plasmid transduction. These phenotypic differences in the vaccines were associated with different functionality, both ex vivo and following administration to patients. Thus adenoviral vaccines induced greater activation of leukemia-reactive T cells ex vivo than plasmid vaccines. In treated patients, specific T-cell (T helper 1 (Th1) and T helper 2 (Th2)) and humoral anti-leukemia responses were detected following administration of the adenoviral vaccine (n = 15), while recipients of the plasmid vaccine (n = 9) manifested only a low-level Th2 response. Progression-free survival at 2 years was 46.7% in the adenoviral vaccine recipients, versus 11.1 % in those receiving plasmid vaccine.
  
  
  CONCLUSIONS
  CLL vaccines expressing the same transgenes but produced by distinct methods of gene transfer may differ in the polarity of the immune response they induce in patients.
authors: Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX 77030, USA. fatvis03@yahoo.com
authors: Fatma Visal
authors: FV
authors: Okur
authors: Eric
authors: E
authors: Yvon
authors: Ettore
authors: E
authors: Biagi
authors: Gianpietro
authors: G
authors: Dotti
authors: George
authors: G
authors: Carrum
authors: Helen
authors: H
authors: Heslop
authors: Martha P
authors: MP
authors: Mims
authors: Joseph C
authors: JC
authors: Fratantoni
authors: Madhusudan V
authors: MV
authors: Peshwa
authors: Linhong
authors: L
authors: Li
authors: Malcolm K
authors: MK
authors: Brenner
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D019496:Cancer Vaccines; D002448:Cell Adhesion; D002454:Cell Differentiation; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics; D014182:Transplantation, Autologous
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007376:Interleukin-2; D023201:CD40 Ligand