Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 12, Issue -, Pages 3566-3575Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/2335
Keywords
multiple myeloma; idiotype; dendritic cells; immunotherapy; mouse model; immune system
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Funding
- NCI NIH HHS [R01S CA96569, CA103978] Funding Source: Medline
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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-gamma 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.
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