Polypeptide-Based K+ Ionophore as a Strong Immunogenic Cell Death Inducer for Cancer Immunotherapy

Immunogenic cell death (ICD) is a key factor for generating antitumor immunity. Endoplasmic reticulum (ER) stress triggers the release of damage-associated molecular patterns (DAMPs), thus inducing immunogenicity. We developed a polypeptide-based K+ ionophore that perturbed ion homeostasis and elici...

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Bibliographic Details
Published in:ACS applied bio materials 2021-12, Vol.4 (12), p.8333-8342
Main Authors: Lee, DaeYong, Ha, JongHoon, Ahn, Hyomin, Jeong, Seong Dong, Jeong, MoonKyoung, Park, Ji-Ho, Yun, Chae-Ok, Kim, Yeu-Chun
Format: Article
Language:English
Subjects:
Alarmins - metabolism
Antineoplastic Agents - pharmacology
Humans
Immunogenic Cell Death
Immunotherapy
Ionophores - pharmacology
Neoplasms - drug therapy
Peptides - therapeutic use
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Summary:Immunogenic cell death (ICD) is a key factor for generating antitumor immunity. Endoplasmic reticulum (ER) stress triggers the release of damage-associated molecular patterns (DAMPs), thus inducing immunogenicity. We developed a polypeptide-based K+ ionophore that perturbed ion homeostasis and elicited a prolonged ER stress. The ER stress not only fosters an oxidative environment that activates mitochondria-dependent apoptosis pathways but also drives immune responses by releasing DAMPs. The ionophore suppressed tumor proliferation in vitro and in vivo based on the pro-apoptotic activity and immunogenicity.
ISSN:2576-6422
2576-6422
DOI:10.1021/acsabm.1c00861