Early vaccination with tumor-lysate-pulsed dendritic cells after allogeneic bone marrow transplantation has antitumor effects.
Allogeneic bone marrow transplantation (BMT) remains the primary treatment for many hematologic malignancies but has had limited success against solid tumors. The antitumor activity of this treatment approach involves the tumoricidal activity of chemoradiation and the additive graft-versus-tumor activity of donor T cells. However, even with current protocols, some tumors develop resistance and become unresponsive to current therapeutic regimens. To address the problem of resistance and lack of solid tumor activity in allogeneic BMT, we undertook experiments to determine whether the graft-versus-tumor activity of donor T cells could be enhanced in the period immediately after allogeneic BMT with tumor lysate-pulsed dendritic cell (DC) vaccines. Using the B16 melanoma model, we found that the treatment of 6-day tumors with allogeneic BMT and 3 weekly vaccinations of tumor lysate-pulsed DCs starting 3 days after BMT had a significant effect on the growth of murine flank melanomas. This effect was tumor specific and occurred in the absence of full immune reconstitution as measured by donor T cell engraftment and cytotoxic T lymphocyte activity. In addition, DC vaccinations did not appear to exacerbate graft-versus-host disease. These experiments support the feasibility of DC vaccine strategies in the setting of allogeneic BMT.
Moyer
Jeffrey S
JS
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-1904, USA. jmoyer@umich.edu
Maine
Gabriel
G
Mulé
James J
JJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D045744:Cell Line, Tumor / Q000637:transplantation; D002478:Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000637:transplantation*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000737:chemistry; D008546:Melanoma, Experimental / Q000601:surgery*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011184:Postoperative Period; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D014020:Tissue Extracts / Q000494:pharmacology*; D014184:Transplantation, Homologous; D014611:Vaccination
D007376:Interleukin-2; D014020:Tissue Extracts; D007371:Interferon-gamma