Fusion of Heat Shock Protein 70 to Antigens Enhances the Potency of DNA Vaccines

Increasing evidence has suggested that CD8+ T cell mediated immune responses are important in controlling both intracellular pathogens and tumors. Using human papillomavirus E7 as a model antigen, we have developed several strategies targeting the MHC class I processing pathway to enhance the CD8+ T cell immune responses and the vaccine potency by linking our model antigen to Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain of pseudomonas aerogenosa exotoxin A (ETA(dII)). The chimeric E7-HSP70, CRT/E7 and ETA(dII)/E7 vaccines generated dramatically enhanced E7-specific CD8+ CTL responses (at least 30 fold compared to vaccines containing the unmodified wild-type E7) and significant anti-tumor effects against an E7-expressing model tumor. These vaccines can be administered as DNA or RNA forms. More recently, we have applied these chimeric HSP70/E7, CRT/E7 and ETA(dII)/E7 strategies to the self-replicating self-limiting RNA replicon system and generate impressive antitumor effects against established lung metastatic tumors. These promising studies have led us to initiate clinical trials scheduled to start in the year 2002. Description (Set) Proposed Use (Set) Therapeutic and prophylactic for cancers associated with HPV specifically cervical cancer. Vaccine may be also used for many other antigens. Patent (Set) WO 01/29233; 6,734,173

Patents:
US 6,734,173

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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