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

Na Kyeong Lee, Jeong Uk Choi, Ha Rin Kim, Seung Woo Chung, Yoon Gun Ko, Young Seok Cho, Seong Jin Park, Eun Jung Lee, Sang Yoon Kim, In San Kim, Youngro Byun

Research output: Contribution to journalArticlepeer-review

Abstract

Here we report a novel combination of a caspase-cleavable peptide-doxorubicin conjugate (MPD-1) with CD47-antagonizing 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 SIRPα-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 IFNγ 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.

Original languageEnglish
Article number121105
JournalBiomaterials
Volume277
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • Caspase-cleavable peptide-doxorubicin conjugate
  • CD47 antagonist
  • Immunotherapy combination
  • MSS colorectal Cancer
  • Nanocage therapeutics

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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