Oncolytic adenoviruses coated with MHC-I tumor epitopes for a new oncolytic vaccine platform
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KeywordsMelanoma Human Melanoma Immunocompetent Mouse Oncolytic Adenovirus Personalized Cancer
Oncolytic adenoviruses (OAds) demonstrated great potential for the treatment of cancer in many pre-clinical studies. The pre-existing immunity and their immunodominance, however, still limit the success of oncolytic virotherapy in cancer patients. Thus, a transition from oncolytic agents to oncolytic vaccines seems to be necessary, since the involment of the immune system may play a key role in the efficacy of OAds.
Therefore, we developed a new oncolytic vaccine platform that uses the virus as adjuvant for MHC-I tumor epitopes that are loaded onto the viral capsid via electrostatic interactions. By using the model epitope SIINFEKL, we studied the efficacy of the peptide-coated conditionally replicating adenoviruses (PeptiCRAds) in immunocompetent mice bearing B16-OVA melanomas.
In conclusion, we demonstrated that the immunogenicity of OAds can be exploited to drive the immune response towards choosen epitopes and that this approach allows for rapid re-targeting without the need of genetic modifications, making PeptiCRAds a suitable platform for the next generation of highly personalized cancer vaccine immunotherapies.
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