A tumor-targeted immune checkpoint blocker.
Zhang. Yuhan Y; Fang. Changming C; Wang. Rongsheng E RE; Wang. Ying Y; Guo. Hui H; Guo. Chao C; Zhao. Lijun L; Li. Shuhong S; Li. Xia X; Schultz. Peter G PG; Cao. Yu J YJ; Wang. Feng F
Key Findings
- The bispecific antibody binds both the melanocortin‑1 receptor and PD‑L1 on melanoma cells
- In a mouse melanoma model it reduced tumor growth more than the parent PD‑L1 antibody at the same dose
- It increased the number of T‑cells infiltrating the tumor microenvironment
Practical Outcomes
- For DIY health enthusiasts this research provides no usable protocol, dosage, or safety guidance. It is an early‑stage cancer therapy tested only in mice and not relevant to longevity, metabolic health, or performance optimization.
Summary
Scientists made a hybrid antibody that attaches a melanin‑stimulating peptide (similar to melanotan‑I) to a PD‑L1 cancer drug, allowing it to target melanoma cells in mice and shrink tumors better than the standard drug alone.
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.
Study Information
pubmed
2019
2019-07-22T00:00:00.000Z
10.1073/pnas.1905646116
22
37