Evidence of B cell immune responses to acute lymphoblastic leukemia in murine allogeneic hematopoietic stem cell transplantation recipients treated with donor lymphocyte infusion and/or vaccination.
These experiments explored mechanisms of control of acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation using a murine model of MHC-matched, minor histocompatibility antigen-mismatched transplantation. The central hypothesis examined was that addition of active vaccination against leukemia cells would substantially increase the effectiveness of allogeneic donor lymphocyte infusion (DLI) against ALL present in the host after transplantation. Although vaccination did increase the magnitude of type I T cell responses against leukemia cells associated with DLI, it did not lead to substantial improvement in long-term survival. Analysis of immunologic mechanisms of leukemia progression demonstrated that the failure of vaccination was not because of antigen loss in leukemia cells. However, analysis of survival provided surprising findings that, in addition to very modest type I T cell responses, a B cell response that produced antibodies that bind leukemia cells was found in long-term survivors. The risk of death from leukemia was significantly lower in recipients that had higher levels of such antibodies. These studies raise the hypothesis that stimulation of B cell responses after transplantation may provide a novel way to enhance allogeneic graft-versus-leukemia effects associated with transplantation.
Mullen
Craig A
CA
Department of Pediatrics, University of Rochester, Rochester, New York, USA. craig_mullen@urmc.rochester.edu
Campbell
Andrew
A
Tkachenko
Olena
O
Jansson
Johan
J
Hsu
Yu-Chiao
YC
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines