NNV024, a novel humanized anti-CD37 antibody with enhanced ADCC and prolonged plasma half-life in human FcRn transgenic mice for treatment of NHL
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Abstract There is an unmet medical need for new therapeutic approaches and targets for patients with non- Hodgkin lymphoma (NHL) who relapse or are refractory to anti-CD20 immunotherapy. Therefore, we developed a humanized IgG 1 antibody targeting CD37, which was tailored to be afucosylated for enhanced antibody-dependent cellular cytotoxicity (ADCC) (NNV024). In line with this, NNV024 induced three-fold more potent ADCC activity against patient-derived chronic lymphocytic leukemia (CLL) cells compared with anti-CD20 obinutuzumab. Moreover, NNV024 showed 2-fold higher ADCC activity than anti-CD20 rituximab and a recombinant version of DuoHexaBody-CD37 against both NHL and CLL cells. Survival was significantly longer after NNV024 treatment than with obinutuzumab in a mouse model. In addition, NNV024 showed a favourable plasma half-life in human FcRn transgenic mice of about 9-days, which was 2-fold longer than that of obinutuzumab and DuoHexaBody-CD37. These results warrant the further development of NNV024 as a treatment for NHL.
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关键词
humanized fcrn transgenic mice,antibody,half-life
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