title: Primary allogeneic T-cell responses against mantle cell lymphoma antigen-presenting cells for adoptive immunotherapy after stem cell transplantation.
abstract: OBJECTIVE
  In patients treated with allogeneic stem cell transplantation for advanced mantle cell lymphoma (MCL), complete sustained remissions have been observed illustrating susceptibility of MCL cells to a graft-versus-lymphoma effect. To potentiate this graft-versus-lymphoma effect, adoptive transfer of in vitro selected MCL-specific CTL can be an attractive approach. The lack of expression of costimulatory molecules on MCL cells hampers the generation of MCL-reactive T-cell responses. The purpose of this study was to modify MCL cells into antigen-presenting cells (APC) and to use these MCL-APCs to induce allogeneic MCL-reactive T-cell responses.
  
  
  METHODS
  Interleukin (IL)-4, IL-10, CpG, and CD40 activation were tested for their capacity to up-regulate costimulatory molecules on MCL cells. Primary MCL cells or the modified MCL-APCs were then used to evaluate the induction of MCL-reactive T-cell responses in HLA-matched donors.
  
  
  RESULTS
  Ligation of CD40 on MCL cells was essential to up-regulate costimulatory molecules and to induce production of high amounts of IL-12. In contrast to primary MCL cells, MCL-APC cells as stimulators were capable of inducing CD8+ CTL lines from HLA class I-matched donors. High numbers of CTL clones could be generated capable of efficiently killing the primary MCL cells and MCL-APC but not donor-specific targets.
  
  
  CONCLUSIONS
  These results show the feasibility to generate primary allogeneic T-cell responses against MCL-APC, and may provide new immunotherapeutic tools to further exploit the graft-versus-lymphoma effect following allogeneic stem cell transplantation in patients with MCL.
authors: Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands. M.Hoogendoorn@lumc.nl
authors: Mels
authors: M
authors: Hoogendoorn
authors: Judith
authors: J
authors: Olde Wolbers
authors: Willem M
authors: WM
authors: Smit
authors: M Ronald
authors: MR
authors: Schaafsma
authors: Inge
authors: I
authors: Jedema
authors: Renee M Y
authors: RM
authors: Barge
authors: Roel
authors: R
authors: Willemze
authors: J H Frederik
authors: JH
authors: Falkenburg
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D020350:Graft vs Tumor Effect; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020522:Lymphoma, Mantle-Cell; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines