Peptide‐Based Cancer Vaccine Delivery via the STINGΔTM‐cGAMP Complex. Issue 15 (19th June 2022)

• Record Type: Journal Article
• Authors: He, Yanpu; Hong, Celestine; Fletcher, Samantha J.; Berger, Adam G.; Sun, Xin; Yang, Mengdi; Huang, Shengnan; Belcher, Angela M.; Irvine, Darrell J.; Li, Jiahe; Hammond, Paula T.
• Is Part Of: Advanced healthcare materials. Volume 11:Issue 15(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-19
• Subjects: cancer immunotherapy -- peptide vaccine delivery -- STING signaling; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202200905
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: 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 (STINGΔTM), then complexing the peptide‐STINGΔTM protein with STING agonist 2'3' cyclic guanosine monophosphate–adenosine monophosphate (cGAMP). The process results in the formation of self‐assembled cGAMP‐peptide‐STINGΔTM tetramers, which enables efficient lymphatic trafficking of the peptide. Moreover, the cGAMP‐STINGΔTM 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. Abstract : Cytosolic stimulator of interferon genes protein‐peptide + 2'3' cyclic guanosine monophosphate–adenosine monophosphate complexes are synthesized via recombinant protein technology for vaccination against cancer. The complexes achieve high levels of vehicle‐free delivery in vitro, antigen presentation ex vivo, and T‐cell priming in vivo. Additionally, they show increased accumulation of adjuvant and epitope peptide in the draining lymph nodes and inhibited tumor growth.