Tumor vaccination strategies combined with autologous peripheral stem cell transplantation.
Despite advances in high-dose therapy with autologous stem cell transplantation for lymphomas, relapse of the underlying disease remains a significant obstacle. Recent advances in cancer vaccine development, specifically, the molecular identification of novel tumor antigens and understanding of cellular signals delivered by cytokines and costimulatory molecules required for efficient T-cell activation, now make it possible to consider combining active specific immunotherapy with PSCT as a strategy for elimination of minimal residual disease. As a model lymphoma-specific antigen, vaccination with patient-specific, immunoglobulin idiotype has been shown to be therapeutically effective when combined with marrow transplantation in small animal models. These preclinical studies predict the feasibility of immunization of human patients with B-cell malignancies vaccinated with this antigen in the post-transplant setting in ongoing clinical trials, especially for T-cell responses. In the future, other vaccine formulations, based on gene therapy approaches to enhance the immunogenicity of whole lymphoma cells or the identification of novel, defined antigens selectively expressed on lymphoma cells, as well as combined strategies of pre- and post-transplant tumor vaccination are envisioned.
Kwak
L W
LW
Department of Experimental Transplantation & Immunology, NCI, Bethesda, MD, USA. kwak@ncifcrf.gov
D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007115:Immunization Schedule; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007165:Immunosuppression Therapy; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D009363:Neoplasm Proteins