A Novel Anti-CD47 Nanobody Tetramer for Cancer Therapy

Autor: Nataliya M. Ratnikova, Yulia Kravchenko, Anna Ivanova, Vladislav Zhuchkov, Elena Frolova, Stepan Chumakov
Jazyk: angličtina
Rok vydání: 2024
Předmět:
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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