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Caspase-cleavable peptide-doxorubicin conjugate in combination with CD47-antagonizing nanocage therapeutics for immune-mediated elimination of colorectal cancer

Authors
Lee, Na KyeongChoi, Jeong UkKim, Ha RinChung, Seung WooKo, Yoon GunCho, Young SeokPark, Seong JinLee, Eun JungKim, Sang YoonKim, In-SanByun, Youngro
Issue Date
10월-2021
Publisher
ELSEVIER SCI LTD
Keywords
CD47 antagonist; Caspase-cleavable peptide-doxorubicin conju-gate; Immunotherapy combination; MSS colorectal Cancer; Nanocage therapeutics
Citation
BIOMATERIALS, v.277
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
277
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/136181
DOI
10.1016/j.biomaterials.2021.121105
ISSN
0142-9612
Abstract
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.
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