Choi, Yoonjeong Nam, Gi-Hoon Kim, Gi Beom Kim, Seohyun Kim, Yoon Kyoung Kim, Seong A. Kim, Ha-Jeong Lee, Eun Jung Kim, In-San 2024-01-19T14:01:13Z 2024-01-19T14:01:13Z 2022-01-10 2021-09 0929-1903 https://pubs.kist.re.kr/handle/201004/116517 Antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), play a crucial role in bridging innate and adaptive immunity; thereby, innate immune checkpoint blockade-based therapy is an attractive approach for the induction of sustainable tumor-specific immunity. The interaction between the cluster of differentiation 47 (CD47) on tumor and signal-regulatory protein alpha (SIRP alpha) on phagocytic cells inhibits the phagocytic function of APCs, acting as a "don't eat me" signal. Accordingly, CD47 blockade is known to increase tumor cell phagocytosis, eliciting tumor-specific CD8(+) T-cell immunity. Here, we introduced a nature-derived nanocage to deliver SIRP gamma for blocking of antiphagocytic signaling through binding to CD47 and combined it with prophagocytic stimuli using a metabolic reprogramming reagent for APCs (CpG-oligodeoxynucleotides). Upon delivering the clustered SIRP gamma variant, the nanocage showed enhanced CD47 binding profiles on tumor cells, thereby promoting active engulfment by phagocytes. Moreover, combination with CpG potentiated the prophagocytic ability, leading to the establishment of antitumorigenic surroundings. This combination treatment could competently inhibit tumor growth by invigorating APCs and CD8(+) T-cells in TMEs in B16F10 orthotopic tumor models, known to be resistant to CD47-targeting therapeutics. Collectively, enhanced delivery of an innate immune checkpoint antagonist with metabolic modulation stimuli of immune cells could be a promising strategy for arousing immune responses against cancer. English SPRINGERNATURE SIGNAL-REGULATORY PROTEIN CD47 BLOCKADE CPG-DNA CELLS ALPHA RECEPTORS TARGET MACROPHAGES ACTIVATION TLR Nanocages displaying SIRP gamma clusters combined with prophagocytic stimulus of phagocytes potentiate anti-tumor immunity Article 10.1038/s41417-021-00372-y 1 CANCER GENE THERAPY, v.28, no.9, pp.960 - 970 CANCER GENE THERAPY 28 9 960 970 scie scopus 000681277300001 2-s2.0-85111711581 Biotechnology & Applied Microbiology Oncology Genetics & Heredity Medicine, Research & Experimental Biotechnology & Applied Microbiology Oncology Genetics & Heredity Research & Experimental Medicine Article SIGNAL-REGULATORY PROTEIN CD47 BLOCKADE CPG-DNA CELLS ALPHA RECEPTORS TARGET MACROPHAGES ACTIVATION TLR