Vaccination Strategies in the Treatment of Lymphomas

Abstract

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.

Expression of Cancer-Testis Genes Prame, Ny-Eso1, Gage1, Mage A3, Mage A6, Mage A12, Ssx1, Sllp1, Pasd1 in Patients With Multiple Myeloma, Their Influence on Overall Survival and Relapse Rate

“…Тем не менее с каждым годом появляется все больше клинических испытаний, ко-торые демонстрируют, что вакцины, содержащие про-дукты экспрессии РТГ, могут вызывать специфический иммунный ответ у больных лимфомами и ММ [22,23].…”

Private Idiotypes Located on Light and Heavy Chains of Human Myeloma Proteins Characterized by Monoclonal Antibodies

“…(8)(9)(10)(11) Successful experimental immunization strategies in animals may 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. (12) Inclusion of immunostimulatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-2 has been shown to enhance therapeutic effectiveness of idiotype vaccination in an animal myeloma model. (9) A synthetic peptide corresponding to the autologous idiotypic variable region heavy chain (VH) complementary determining region (CDR3) sequence has also been reported to elicit peptide specific immune responses in human myeloma.…”

Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma

“…4 The need for new treatment modalities has driven evaluation of various immunotherapies including recombinant human interferon-␣ (IFN-␣), 5 monoclonal antibody targeting (CD20, CD19, CD22) 6 or anti-tumor vaccines. 7 The idiotype (Id), a unique surface immunoglobulin expressed by B cell lymphoma, is considered a suitable specific tumor associated antigen for vaccination. 8 The Id is a weakly immunogenic self-antigen and immuno-modulation by fusion to more immunogenic antigens has been shown to enhance its immunogenicity.…”