Autor: |
Nataliya M. Ratnikova, Yulia Kravchenko, Anna Ivanova, Vladislav Zhuchkov, Elena Frolova, Stepan Chumakov |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Antibodies, Vol 13, Iss 1, p 2 (2024) |
Druh dokumentu: |
article |
ISSN: |
2073-4468 |
DOI: |
10.3390/antib13010002 |
Popis: |
CD47 acts as a defense mechanism for tumor cells by sending a “don’t eat me” signal via its bond with SIRPα. With CD47’s overexpression linked to poor cancer outcomes, its pathway has become a target in cancer immunotherapy. Though monoclonal antibodies offer specificity, they have limitations like the large size and production costs. Nanobodies, due to their small size and unique properties, present a promising therapeutic alternative. In our study, a high-affinity anti-CD47 nanobody was engineered from an immunized alpaca. We isolated a specific VHH from the phage library, which has nanomolar affinity to SIRPα, and constructed a streptavidin-based tetramer. The efficacy of the nanobody and its derivative was evaluated using various assays. The new nanobody demonstrated higher affinity than the monoclonal anti-CD47 antibody, B6H12.2. The nanobody and its derivatives also stimulated substantial phagocytosis of tumor cell lines and induced apoptosis in U937 cells, a response confirmed in both in vitro and in vivo settings. Our results underscore the potential of the engineered anti-CD47 nanobody as a promising candidate for cancer immunotherapy. The derived nanobody could offer a more effective, cost-efficient alternative to conventional antibodies in disrupting the CD47–SIRPα axis, opening doors for its standalone or combinatorial therapeutic applications in oncology. |
Databáze: |
Directory of Open Access Journals |
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