Second-Generation Therapeutic DNA Lymphoma Vaccines
Annual rept. 15 Apr 2008-14 Apr 2009
M D ANDERSON CANCER CENTER HOUSTON TX
Pagination or Media Count:
Lymphoma idiotype DNA vaccines have shown their therapeutic potential in preclincial studies however, vaccine-induced anti-tumor effects need to be improved for translation of the vaccines into clinical use. Here we show that chemokine-fused idiotype DNA vaccines, when combined with cardiotoxin, which induced cellular infiltration at vaccination sites, were exceptional in their ability to provoke antitumor immunity in mice. The combined vaccination strategy significantly mounted both idiotype-specific T-cell responses and humoral immunity. Unexpectedly, vaccine-induced tumor protection was found to be intact in B-cell deficient mice, but was abrogated completely in T-cell-depleted mice. This is the first evidence showing that antibody response is not the immune mechanism for vaccine-induced tumor killing, supporting the significance of inducing T-cell immunity in designing idiotype vaccines. The potent immunostimulatory effect of myotoxins was immune-mediated, requiring recruitment of antigen-presenting cells for memory T-cell responses. These preclinical data highlight the translational potential of this novel idiotype DNA vaccine therapy against lymphoma.
- Medicine and Medical Research