Yuhan Zhang, Changming Fang, Rongsheng E. Wang, Ying Wang, Hui Guo, Chao Guo, Lijun Zhao, Shuhong Li, Xia Li, Peter G. Schultz, Yu J. Cao, and Feng Wang
Abstract
To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, D-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors.
附件下载：
A tumor-targeted immune checkpoint blocker, PNAS, 22 Jul 2019
PNAS, July, 2019, DOI: https://doi.org/10.1073/pnas.1905646116
A tumor-targeted immune checkpoint blocker
Yuhan Zhang, Changming Fang, Rongsheng E. Wang, Ying Wang, Hui Guo, Chao Guo, Lijun Zhao, Shuhong Li, Xia Li, Peter G. Schultz, Yu J. Cao, and Feng Wang
Abstract
To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, D-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors.
文章链接：https://www.pnas.org/content/early/2019/07/11/1905646116
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