Vaccination strategies in the treatment of lymphomas.
Malignant lymphomas are clonal neoplasms of lymphoid origin. By definition, all cells of the malignant clone have undergone the same rearrangement of antigen receptor genes and express identical antigen receptor molecules (immunoglobulin for B cell lymphomas, T cell receptor for T cell lymphomas). The hypervariable stretches within the variable regions of these receptors are considered true tumor-specific antigens ('idiotypes'). In several animal models, protective humoral or cellular immunity can be induced against the malignant lymphoma by vaccination with the tumor-derived idiotype. Successful experimental immunization strategies in animals include idiotype protein vaccines combined with various adjuvants, genetically or immunologically modified lymphoma cells, idiotype-presenting dendritic cells, idiotype-encoding viral vectors, and DNA immunization. Firm evidence for the induction of lymphoma-specific immunity has also been obtained from human idiotype vaccination trials. Furthermore, some trials have provided strong but hitherto formally unproven evidence for clinical benefit of idiotype-vaccinated patients. Alternative vaccination approaches are based on immunologically modified tumor cells. Current research efforts concentrate on the identification of the most efficacious vaccination route, on definitive proof of clinical efficacy, and on the development of convenient methods to manufacture individual idiotype vaccines.
Veelken
Hendrik
H
Department of Internal Medicine I, Freiburg University Medical Center, Germany. veelken@mm11.ukl.uni-freiburg.de
Osterroth
Frank
F
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005544:Forecasting; D006801:Humans; D007130:Immunoglobulin Idiotypes; D007167:Immunotherapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes