Comparing Murine PD-1 and PD-L1 Monoclonal Antibodies for Cancer Immunotherapy Research
Researchers from the Dana-Farber Cancer Institute and Harvard Medical School have conducted a comprehensive comparison of commonly used monoclonal antibodies (mAbs) targeting the PD-1/PD-L1 pathway in mice. Their findings, recently published in the journal Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, provide valuable insights for modeling cancer immunotherapy in preclinical studies.
The PD-1/PD-L1 pathway is a critical immune checkpoint that can be exploited by cancer cells to evade the immune system. Blocking this pathway with mAbs has proven to be an effective cancer immunotherapy strategy, with several FDA-approved antibodies already in clinical use. To better understand and optimize these therapies, researchers often use mouse models and anti-mouse PD-1 and PD-L1 mAbs.
In this study, the scientists compared the binding affinities, blocking capacities, and biological activities of the most widely used anti-mouse PD-1 mAbs (29F.1A12, RMP1-14, and RMP1-30) and anti-mouse PD-L1 mAbs (10F.9G2 and MIH6). They also provided the amino acid sequences of 10F.9G2 and 29F.1A12 to facilitate further research and development.
Key findings:
1. PD-L1 mAbs 10F.9G2 and MIH6 exhibited similar binding affinities and blocking capacities, suggesting they are nearly equivalent in their properties.
2. PD-1 mAb 29F.1A12 demonstrated a significantly higher binding affinity and blocking capacity compared to RMP1-14, indicating that 29F.1A12 more closely mimics the properties of human therapeutic antibodies.
3. RMP1-30 was unable to block the PD-1/PD-L1 interaction and did not enhance T cell activation, consistent with previous reports.
4. The epitope binding regions of these mAbs were characterized, revealing that 29F.1A12, RMP1-14, and RMP1-30 recognize distinct but overlapping epitopes on PD-1.
5. The study also identified an alternative mAb (10F.5C5) that can be used to analyze PD-L1 expression in the presence of 10F.9G2 or MIH6, which could be useful for monitoring therapeutic responses.
The researchers concluded that using 29F.1A12 in mouse tumor immunotherapy experiments more closely models the high-affinity, blocking characteristics of FDA-approved human therapeutic mAbs. They also suggest that using RMP1-14 in combination immunotherapy studies may underestimate the potency of the second agent due to its lower affinity and less persistent PD-1 blockade.
This study provides a valuable resource for researchers working with mouse models of cancer immunotherapy. The comprehensive characterization of these mAbs and the provision of 10F.9G2 and 29F.1A12 sequences will help scientists design more accurate and translationally relevant preclinical studies, ultimately leading to the development of improved immunotherapies for cancer patients.