Finally, we show that severe autoimmunity by BiVax/IL2Cx was prevented while preserving outstanding antitumor responses by utilizing a tumor antigen not expressed in the pancreas.
To date more than 110 genetic variants have been firmly associated to an increased risk of developing MS. A large part of these variants tag genes involved in the regulation of immune response and several of them are shared with other autoimmune diseases, suggesting a common etiological root for this class of disorders.
Therefore, we developed a novel CTLA4 mutant that could be expressed in tumor antigen-specific T cells to enhance antitumor effect without systemic autoimmunity.
We hypothesized that local delivery of anti-CTLA-4 and anti-GITR mAbs to the sites where T cells and tumor antigen-loaded DC vaccines interact would enhance the induction of anti-tumor immunity while avoiding autoimmunity.
Early-stage clinical testing raises the possibility that combinatorial approaches that augment dendritic cell-mediated tumor antigen presentation and antagonize negative immune regulation may accomplish significant tumor destruction without the induction of serious autoimmune disease.