afucosylated-IgG1 variant of avelumab有点意思
发表于 ： 3月 5, 2023, 3:06 pm
Happy to share our new study on the role of Fc Receptors in antitumor activity of human PD-L1 mAbs and the generation of Fc-optimized PD-L1 mAb for #cancer #immunotherapy .
In this study, led by Noy Cohen, we investigated the contribution of the IgG Fc scaffolds of FDA-approved anti-PD-L1 mAbs (avelumab, atezolizumab, durvalumab) and found that these mAbs don’t lead to efficient engagement of beneficial FcgR pathways. This allowed us to rationally modify their Fc to enhance their therapeutic efficacy. Such Fc-optimized anti-PD-L1 mAb (afucosylated-IgG1 variant of avelumab) leads to elimination of PD-L1+ myeloid-derived suppressor cells (MDSC) in the tumor, reducing the immune suppression in the tumor microenvironment. This stimulates infiltration and activation of cytotoxic and effector T cells. In a second wave of response, neutrophils frequency increases in the TME and they undergo significant phenotypic changes empowering them with variety of pro-inflammatory activities.
In this study, led by Noy Cohen, we investigated the contribution of the IgG Fc scaffolds of FDA-approved anti-PD-L1 mAbs (avelumab, atezolizumab, durvalumab) and found that these mAbs don’t lead to efficient engagement of beneficial FcgR pathways. This allowed us to rationally modify their Fc to enhance their therapeutic efficacy. Such Fc-optimized anti-PD-L1 mAb (afucosylated-IgG1 variant of avelumab) leads to elimination of PD-L1+ myeloid-derived suppressor cells (MDSC) in the tumor, reducing the immune suppression in the tumor microenvironment. This stimulates infiltration and activation of cytotoxic and effector T cells. In a second wave of response, neutrophils frequency increases in the TME and they undergo significant phenotypic changes empowering them with variety of pro-inflammatory activities.