A tumor-targeted immune checkpoint blocker

Yuhan Zhang, Changming Fang, Rongsheng E. Ross, Ying Wang, Hui Guo, Chao Guo, Lijun Zhao, Shuhong Li, Xia Li, Peter G. Schultz, Yu J. Cao, Feng Wang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)15889-15894
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number32
DOIs
StatePublished - Aug 6 2019

Keywords

  • Bispecific antibody
  • Immunotherapy
  • Melanoma
  • PD-L1 inhibitor

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