Lee, Na Kyeong Choi, Jeong Uk Kim, Ha Rin Chung, Seung Woo Ko, Yoon Gun Cho, Young Seok Park, Seong Jin Lee, Eun Jung Kim, Sang Yoon Kim, In-San Byun, Youngro 2024-01-19T13:33:57Z 2024-01-19T13:33:57Z 2022-01-10 2021-10 0142-9612 https://pubs.kist.re.kr/handle/201004/116335 Here we report a novel combination of a caspase-cleavable peptide-doxorubicin conjugate (MPD-1) with CD47antagonizing nanocage therapeutics for the treatment of microsatellite-stable (MSS) colorectal cancer (CRC). MPD-1 (i) upregulated markers of immunogenic cell death (ICD) in tumor, and increased co-stimulatory markers on dendritic cells (DCs), (ii) enhanced CD8+ T cell infiltration and antigen presenting cell (APC) activation, and (iii) showed negligible off-target immune-related toxicity compared to free dox. Then, the CD47 antagonist FS nanocage, a SIRP alpha-expressing ferritin nanocage, was co-administered with MPD-1 that resulted in 95.2% (p < 0.001) tumor growth inhibition in an established CRC model. T cell-mediated elimination of tumors was also confirmed by the tumor-specific activation of T cells detected by IFN gamma and tumor-free mice were observed (95%) that bared a memory response when re-challenged. The strategically developed MPD-1 is an ideal adjuvant to immunotherapy and the combination with FS nanocage triggers potent immunity against MSS CRC. In summary, we present an approach to initiate and stimulate immune-mediated eradication of cancer cells using synergistic immunogenic agents targeting the MSS CRC. English ELSEVIER SCI LTD IMMUNOGENIC CELL-DEATH IMMUNOTHERAPY CHEMOTHERAPY TUMORS Caspase-cleavable peptide-doxorubicin conjugate in combination with CD47-antagonizing nanocage therapeutics for immune-mediated elimination of colorectal cancer Article 10.1016/j.biomaterials.2021.121105 1 BIOMATERIALS, v.277 BIOMATERIALS 277 scie scopus 000697767000001 2-s2.0-85113911758 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article IMMUNOGENIC CELL-DEATH IMMUNOTHERAPY CHEMOTHERAPY TUMORS Caspase-cleavable peptide-doxorubicin conju-gate Nanocage therapeutics CD47 antagonist Immunotherapy combination MSS colorectal Cancer