Therapeutic PD-L1 antibodies are more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling

Abstract

Inhibitors of PD-1 signaling have revolutionized cancer therapy. PD-1 and PD-L1 antibodies have been approved for the treatment of cancer. To date, therapeutic PD-1 inhibitors have not been compared in a functional assay. We used an efficient T cell reporter platform to evaluate the efficacy of five clinically used PD-1 inhibitors to block PD-1 signaling. The half maximal effective concentrations (EC 50 ) for nivolumab and pembrolizumab were 76.17 ng/ml (95% CI 64.95–89.34 ng/ml) and 39.90 ng/ml (34.01–46.80 ng/ml), respectively. The EC 50 values of the PD-L1 inhibitors were 6.46 ng/ml (5.48–7.61 ng/ml), 6.15 ng/ml (5.24–7.21 ng/ml) and 7.64 ng/ml (6.52–8.96 ng/ml) for atezolizumab, avelumab, and durvalumab, respectively. In conclusion, a functional assay evaluating antibodies targeting PD-1 inhibition in vitro revealed that pembrolizumab is a slightly more effective PD-1 blocker than nivolumab, and that PD-L1 antibodies are superior to PD-1 antibodies in reverting PD-1 signaling.

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

“…Recent in vitro studies suggest that differences between receptor- vs. ligand-based antagonism may exist and have implications for combination treatments. In a study using a functional T-cell in vitro assay, PD-L1 antibodies were found to be more effective than PD-1 antibodies in inhibiting PD-1 signaling ( 215 ). A study using in vivo murine breast and colon cancer models showed that anti–PD-L1 (but not anti–PD-1) monotherapy was able to deplete CD80 ligand expression on tumor-infiltrating antigen-presenting cells, thereby inhibiting CTLA-4 axis through a Treg-dependent mechanism ( 216 ).…”

Shortwave-infrared (SWIR) fluorescence molecular imaging using indocyanine green–antibody conjugates for the optical diagnostics of cancerous tumours

“…As tumour-targeting probes, we used four types of monoclonal antibodies such as anti-HER2 antibody (Herceptin), 20 anti-EGFR antibody (Erbitux), 21 anti-VEGFR-2 antibody (Cyramza), 22 and anti-PD-L1 antibody (anti-PD-L1 ab). 23 These monoclonal antibodies are used as antibody drugs of cancer therapy for breast and skin tumours in clinical elds. By using the ICG-antibody conjugates, we conducted NIR and SWIR uorescence imaging of breast and skin tumours in mice.…”

Transferrin receptor 1 is a cellular receptor for human heme-albumin

“…In some experiments, cells were pretreated with different antibodies or proteins like CD71 mAbs (5 µg/ml), transferrin (50 µg/ml), Abraxane (100 ng/ml), HSA or HSA-heme (both 200 µg/ml). K D value for HSA-heme was calculated as described 61 . Flow cytometry analyses were performed using FACSCalibur flow cytometer (Becton Dickinson, Franklin Lakes, NJ).…”