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The anti-B7-H3 blocking antibody MJ18 does not recognize B7-H3 in murine tumor models

The immune checkpoint molecule B7-H3 is regarded as one of the most promising therapeutic targets for the treatment of human cancers. B7-H3 is highly expressed in many cancers and its expression has been associated to impaired antitumor immunity and poor patient prognosis. In immunocompetent mouse t...

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Detalles Bibliográficos
Autores principales: Nammor, Talah, Frizzell, Jenna, Lavoie, Roxane R., Lucien, Fabrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680724/
https://www.ncbi.nlm.nih.gov/pubmed/38014341
http://dx.doi.org/10.1101/2023.11.15.567261
Descripción
Sumario:The immune checkpoint molecule B7-H3 is regarded as one of the most promising therapeutic targets for the treatment of human cancers. B7-H3 is highly expressed in many cancers and its expression has been associated to impaired antitumor immunity and poor patient prognosis. In immunocompetent mouse tumor models, genetic deletion of B7-H3 in tumor cells enhances antitumor immune response leading to tumor shrinkage. The underlying mechanisms of B7-H3 inhibitory function remain largely uncharacterized and the identity of potential cognate(s) receptor(s) of B7-H3 is still to be defined. To better understand B7-H3 function in vivo, several studies have employed MJ18, a monoclonal antibody reported to bind murine B7-H3 and blocks its immune-inhibitory function. In this brief research report, we show that 1) MJ18 does not bind B7-H3, 2) MJ18 binds the Fc receptor FcγRIIB on surface of murine splenocytes, and 3) MJ18 does not induce tumor regression in a mouse model responsive to B7-H3 knockout. Given the high profile of B7-H3 as therapeutic target for human cancers, our work emphasizes that murine B7-H3 studies using the MJ18 antibody should be interpreted with caution. Finally, we hope that our study will motivate the scientific community to establish much-needed validated research tools to study B7-H3 biology in mouse models.