Dendritic cell vaccine but not idiotype-KLH protein vaccine primes therapeutic tumor-specific immunity against multiple myeloma.
Idiotype protein (Id) secreted by myeloma cells is the best-characterized tumor-specific antigen and is widely used in clinical trials of immunotherapy in B-cell tumors. In this study, we used a myeloma murine model to compare the efficacy of two commonly used vaccines in human trials, Id-keyhole limpet hemocyanin (KLH) protein versus Id-KLH-pulsed DC vaccines in preventing or treating myeloma and priming tumor-specific immune responses. Although both vaccines were able to protect mice from developing myeloma, only the DC vaccine induced therapeutic immunity in tumor-bearing mice. DC vaccinations not only retarded tumor growth but also eradicated established myeloma in 60% of mice. The therapeutic efficacy of the DC vaccine was associated with increased tumor-specific IFN-g and IL-4 T-cell responses and cytolytic activity of splenic T cells. Moreover, the vaccines induced tumor-specific immune responses that protected surviving mice from tumor rechallenge. Thus, our results demonstrate that Id-based DC vaccine but not Id-KLH protein vaccine can be therapeutic to established myeloma. Further studies are needed to optimize methods of DC-based vaccines to improve the efficacy of clinical trials.
Wang
Siqing
S
Department of Lymphoma and Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer, Houston, Texas 77030, USA.
Hong
Sungyoul
S
Wezeman
Michele
M
Qian
Jianfei
J
Yang
Jing
J
Yi
Qing
Q
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy
D019496:Cancer Vaccines