Therapeutic lymphoma vaccines: importance of T-cell immunity.
The unique antigenic determinants, termed idiotype, of the immunoglobulin expressed on a given B-cell malignancy can serve as a tumor-specific antigen for active immunotherapy. Administration of autologous tumor-derived idiotype protein conjugated to a carrier protein, keyhole limpet hemocyanin, together with granulocyte-macrophage colony-stimulating factor to follicular lymphoma patients in complete clinical remission was associated with induction of tumor-specific cellular and humoral immunity, molecular remissions, and prolonged disease-free survival. Idiotype vaccination in patients with mantle cell lymphoma following rituximab-containing chemotherapy induced tumor-specific T-cell immunity in the absence of B cells, suggesting that vaccines may be used in combination with rituximab. Three double-blind, randomized, Phase III idiotype vaccine trials are currently ongoing to definitively determine the clinical benefit of idiotype-keyhole limpet hemocyanin plus granulocyte-macrophage colony-stimulating factor vaccination in patients with lymphoma. Results from early clinical trials with idiotype vaccines suggested that both humoral and cellular immune responses may be independently associated with tumor regression and improved progression-free survival. With the increased use of rituximab for the treatment of follicular lymphoma and other B-cell non-Hodgkin's lymphomas, further improvement in the potency of the vaccines would require strategies to enhance T-cell responses, as rituximab depletes normal B cells and impairs the generation of antibody responses.
Neelapu
Sattva S
SS
UT MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Unit 903, 7455 Fannin, Houston, TX 77054, USA. sneelapu@mdanderson.org
Lee
Seung-Tae
ST
Qin
Hong
H
Cha
Soung-Chul
SC
Woo
Alison F
AF
Kwak
Larry W
LW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D000069283:Rituximab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor