Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment

Tae Heung Kang, Jung Hwa Park, Andrew Yang, Hyun Jin Park, Sung Eun Lee, Young Seob Kim, Gun-Young Jang, Emily Farmer, Brandon Lam, Yeong-Min Park () and Chien-Fu Hung ()
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Tae Heung Kang: School of Medicine, Konkuk University
Jung Hwa Park: School of Medicine, Konkuk University
Andrew Yang: Medical Scientist Training Program, Baylor College of Medicine
Hyun Jin Park: School of Medicine, Konkuk University
Sung Eun Lee: School of Medicine, Konkuk University
Young Seob Kim: School of Medicine, Konkuk University
Gun-Young Jang: School of Medicine, Konkuk University
Emily Farmer: Department of Pathology, Johns Hopkins Medical Institutions
Brandon Lam: Graduate Program in Immunology, Department of Pathology, Johns Hopkins Medical Institutions
Yeong-Min Park: School of Medicine, Konkuk University
Chien-Fu Hung: Department of Pathology, Department of Oncology, Johns Hopkins Medical Institutions

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The interaction between immune cells and phosphatidylserine (PS) molecules exposed on the surface of apoptotic-tumor bodies, such as those induced by chemotherapies, contributes to the formation of an immunosuppressive tumor microenvironment (TME). Annexin A5 (AnxA5) binds with high affinity to PS externalized by apoptotic cells, thereby hindering their interaction with immune cells. Here, we show that AnxA5 administration rescue the immunosuppressive state of the TME induced by chemotherapy. Due to the preferential homing of AnxA5 to the TME enriched with PS+ tumor cells, we demonstrate in vivo that fusing tumor-antigen peptide to AnxA5 significantly enhances its immunogenicity and antitumor efficacy when administered after chemotherapy. Also, the therapeutic antitumor effect of an AnxA5-peptide fusion can be further enhanced by administration of other immune checkpoint inhibitors. Our findings support the administration of AnxA5 following chemotherapy as a promising immune checkpoint inhibitor for cancer treatment.

Date: 2020
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DOI: 10.1038/s41467-020-14821-z

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