Peptide-Based Cancer Vaccine Delivery via the STINGΔTM-cGAMP Complex

With the advent of bioinformatic tools in efficiently predicting neo-antigens, peptide vaccines have gained tremendous attention in cancer immunotherapy. However, the delivery of peptide vaccines remains a major challenge, primarily due to ineffective transport to lymph nodes and low immunogenicity. Here, a strategy for peptide vaccine delivery is reported by first fusing the peptide to the cytosolic domain of the stimulator of interferon genes protein (STING Delta TM), then complexing the peptide-STING Delta TM protein with STING agonist 2'3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). The process results in the formation of self-assembled cGAMP-peptide-STING Delta TM tetramers, which enables efficient lymphatic trafficking of the peptide. Moreover, the cGAMP-STING Delta TM complex acts not only as a protein carrier for the peptide, but also as a potent adjuvant capable of triggering STING signaling independent of endogenous STING protein-an especially important attribute considering that certain cancer cells epigenetically silence their endogenous STING expression. With model antigen SIINFEKL, it is demonstrated that the platform elicits effective STING signaling in vitro, draining lymph node targeting in vivo, effective T cell priming in vivo as well as antitumoral immune response in a mouse colon carcinoma model, providing a versatile solution to the challenges faced in peptide vaccine delivery.

Automated summary

By fusing the peptide with STING Delta TM and complexing it with cGAMP, self-assembled cGAMP-peptide-STING Delta TM tetramers are formed, enabling efficient lymphatic trafficking of the peptide. This strategy acts as a protein carrier for the peptide and a potent adjuvant capable of triggering STING signaling, effectively addressing the challenges in peptide vaccine delivery.