Anti-angiogenesis targeted vaccine therapy

VEGF receptor 2 (R2) is expressed mainly on proliferating endothelial cells, and plays an important role in tumor growth and metastasis. Thus, developing a CTL response might inhibit tumor angiogenesis. Therefore, we have identified several MHC Class I binding sequences from murine and human VEGF R2. We found that these peptides exhibit high binding affinity to HLA-A2, can induce specific T cell activation measured by IFN-gamma production and CTL able to lyse VEGF R2 expressing cells lines, and can eliminate endothelial cells expressing the VEGF R2 in an animal tumor model and decrease tumor growth. This work was published in 06. We further built on that by developing an enhanced strategy for utilizing whole endothelial cell line modified with an immune enhancing molecule LIGHT. We found that by utilizing these endothelial cell lines expressing the LIGHT protein that we generate specific immune response against endothelial cells which lead to the inhibition of angiogenesis. Furthermore, we found that this strategy can inhibit the growth of melanoma tumor. This manuscript will be submitted for publication. Currently, we are also testing the combination of anti endothelial vaccine approach with small molecules targeting the tyrosine kinase moiety of the VEGFR2 receptor.