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

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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.
Author(s)
고윤건김상윤김인산김하린박성진변영로이나경이은정정승우조영석최정욱
Issued Date
2021
Type
Article
Keyword
CD47 antagonistCaspase-cleavable peptide-doxorubicin conjugateImmunotherapy combinationMSS colorectal CancerNanocage therapeutics.
DOI
10.1016/j.biomaterials.2021.121105
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8379
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2569379929&amp;context=PC&amp;vid=ULSAN&amp;lang=ko_KR&amp;search_scope=default_scope&amp;adaptor=primo_central_multiple_fe&amp;tab=default_tab&amp;query=any,contains,Caspase-cleavable%20peptide-doxorubicin%20conjugate%20in%20combination%20with%20CD47-antagonizing%20nanocage%20therapeutics%20for%20immune-mediated%20elimination%20of%20colorectal%20cancer&amp;offset=0&amp;pcAvailability=true
Publisher
BIOMATERIALS
Location
영국
Language
한국어
ISSN
0142-9612
Citation Volume
277
Citation Number
1
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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