m276-SL-PBD

m276-SL-PBD is an experimental antibody-drug conjugate (ADC) developed by researchers at the National Cancer Institute (NCI) to target B7-H3 (CD276), a cell surface protein that is frequently overexpressed in various aggressive malignancies, including small cell lung cancer (SCLC). The ADC is composed of the humanized monoclonal antibody m276, which specifically binds to B7-H3, conjugated to a potent pyrrolobenzodiazepine (PBD) dimer payload via a linker (designated as SL). B7-H3 serves as both an immune checkpoint molecule that suppresses T-cell activation and an oncogenic driver that promotes tumor progression and metastasis. Upon binding to B7-H3 on the tumor cell surface, m276-SL-PBD is internalized, leading to the intracellular release of the PBD payload. The PBD dimer then binds to the minor groove of DNA and forms interstrand cross-links, which results in DNA damage, cell cycle arrest, and apoptosis. Preclinical studies in spontaneous SCLC mouse models have demonstrated that m276-SL-PBD significantly reduces tumor burden, inhibits metastasis and angiogenesis, and enhances T-cell infiltration into the tumor microenvironment, potentially by modulating the expression of metastatic drivers like NFIB.

Other names

m276-PBDm-276-PBDm 276-PBDanti-B7-H3 ADCanti-B-7-H3 ADCanti-B 7-H3 ADCCD276 ADCCD-276 ADCCD 276 ADC