Fusion of Calreticulun (CRT) to Antigens Enhances the Potency of DNA Vaccines

Antigen-specific cancer immunotherapy and anti-angiogenesis have emerged as two attractive strategies for cancer treatment. An innovative approach that combines both mechanisms will likely generate the most potent anti-tumor effect. In this study, we tested this notion using calreticulin (CRT) since it has been shown to be able to enhance MHC class I presentation and exhibit an anti-angiogenic effect. We explored the linkage of CRT to a model tumor antigen, human papillomavirus type-16 (HPV-16) E7, for the development of a DNA vaccine. We found that mice vaccinated intradermally with a chimeric CRT/E7 DNA vaccine exhibited a dramatic increase in E7-specific CD8+ T cell precursors and an impressive anti-tumor effect compared to mice vaccinated with wild-type E7 DNA or CRT DNA vaccines. In order to determine if anti-angiogenesis contributed to the anti-tumor effect of chimeric CRT/E7 DNA, we treated lung tumors in immunocompromised mice using various DNA constructs and found that CRT/E7 DNA and CRT DNA generated significant reduction of lung tumor nodules and decreased the microvessel density within lung tumor nodules compared to wild-type E7 DNA. An in vivo angiogenesis assay using Matrigel further confirmed the anti-angiogenic effect generated by CRT/E7 and CRT. Our results suggest that cancer therapy using CRT linked to a tumor antigen may be an attractive strategy for treating tumors by combining antigen-specific immunotherapy and anti-angiogenesis. Description (Set) Proposed Use (Set) The technology may be used for the development of preventive and therapeutic vaccines for infectious diseases and cancers in human and animals.

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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