Koh, Eunee Lee, Eun Jung Nam, Gi-Hoon Hong, Yeonsun Cho, Eunji Yang, Yoosoo Kim, In-San 2024-01-20T02:02:23Z 2024-01-20T02:02:23Z 2021-09-01 2017-03 0142-9612 https://pubs.kist.re.kr/handle/201004/122996 CD47, a "don't eat me" signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein alpha (SIRP alpha) on phagocytic cells. By engaging SIRP alpha, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRP alpha. These exosomes harboring SIRP alpha variants (SIRP alpha-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRP alpha on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRP alpha interaction by SIRP alpha-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRP alpha-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRP alpha proteins could effectively lead to phagocytic elimination of tumor cells both in vitro and in vivo. Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics. (C) 2017 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD LEUKEMIA STEM-CELLS DRUG-DELIVERY GROWTH-FACTOR MACROPHAGES MECHANISM PACLITAXEL VESICLES VEHICLES THERAPY BINDING Exosome-SIRP alpha, a CD47 blockade increases cancer cell phagocytosis Article 10.1016/j.biomaterials.2017.01.004 1 BIOMATERIALS, v.121, pp.121 - 129 BIOMATERIALS 121 121 129 scie scopus 000393933000010 2-s2.0-85009127198 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article LEUKEMIA STEM-CELLS DRUG-DELIVERY GROWTH-FACTOR MACROPHAGES MECHANISM PACLITAXEL VESICLES VEHICLES THERAPY BINDING Exosome Cancer immunotherapy CD47 Signal regulatory protein alpha Phagocytosis