Peptide‐Based Cancer Vaccine Delivery via the STINGΔTM‐cGAMP Complex
Name
Adv Healthcare Materials - 2022 - He - Peptide‐Based Cancer Vaccine Delivery via the STING TM‐cGAMP Complex.pdf
Description
Published version
Size
1.94 MB
Format
Adobe PDF
Checksum (MD5)
85f775ee0bd5687f5608157456ec3146
Author(s)
He, Yanpu
Hong, Celestine
Fletcher, Samantha J
Berger, Adam G
Sun, Xin
Yang, Mengdi
Huang, Shengnan
Belcher, Angela M
Irvine, Darrell J
Li, Jiahe
Date Issued
August 2022
Journal
Advanced Healthcare Materials
Publisher
Wiley
Citation
He, Yanpu, Hong, Celestine, Fletcher, Samantha J, Berger, Adam G, Sun, Xin et al. 2022. "Peptide‐Based Cancer Vaccine Delivery via the STINGΔTM‐cGAMP Complex." Advanced Healthcare Materials, 11 (15).
Version
Final published version
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/adhm.202200905
