Journal
MABS
Volume 14, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2022.2088454
Keywords
PD-1; antibody; affinity; pharmacokinetic modeling; cancer immunotherapy
Categories
Ask authors/readers for more resources
Monoclonal antibodies targeting PD-1 show varied efficacy depending on their affinity, and a threshold affinity is required for maximum efficacy in the treatment of MC38 adenocarcinoma.
Monoclonal antibodies targeting the programmed cell death protein 1 (PD-1) remain the most prevalent cancer immunotherapy both as a monotherapy and in combination with additional therapies. Despite the extensive success of anti-PD-1 monoclonal antibodies in the clinic, the experimental relationship between binding affinity and functional potency for anti-PD-1 antibodies in vivo has not been reported. Anti-PD-1 antibodies with higher and lower affinity than nivolumab or pembrolizumab are entering the clinic and show varied preclinical efficacy. Here, we explore the role of broad-ranging affinity variation within a single lineage in a syngeneic immunocompetent mouse model. By developing a panel of murine anti-PD-1 antibodies with varying affinity (ranging from K-D = 20 pM - 15 nM), we find that there is a threshold affinity required for maximum efficacy at a given dose in the treatment of the MC38 adenocarcinoma model with anti-PD-1 immunotherapy. Physiologically based pharmacokinetic modeling complements interpretation of the experimental results and highlights the direct relationship between dose, affinity, and PD-1 target saturation in the tumor.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available