Journal
CANCER MEDICINE
Volume 10, Issue 6, Pages 2125-2136Publisher
WILEY
DOI: 10.1002/cam4.3768
Keywords
antitumor drug; CD47; peptide; SIRPα targeted therapy
Categories
Funding
- National Science and Technology Major Projects of New Drugs [2019ZX09301124, 2019ZX09201001, 2019ZX09301-110]
- Project Program of the State Key Laboratory of Natural Medicines [SKLNMZZCX201821]
- Open Project of State Key Laboratory of Natural Medicines [SKLNMKF202008]
- Natural Science Foundation of Jiangsu Province, China [BK20180569]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Double First-Class University project [CPU2018GY13, CPU2018PZH03]
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The study designed and synthesized a peptide that can specifically bind to CD47 and block signaling pathways. Results showed that the peptide promoted phagocytosis of tumor cells by macrophages, demonstrating therapeutic effects in vitro and in vivo. RS17 may represent a novel therapeutic peptide for cancer therapy.
Background CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a Don't eat me signal by interacting with SIRP alpha on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRP alpha has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated. Methods We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47-SIRP alpha signaling. The affinity of RS17 for CD47-expressing tumor cells was determined, while the inhibition of CD47-SIRP alpha signaling was evaluated in vitro and in vivo. Results The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47-expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth. Conclusions Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy.
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