Enhancing Tumor Immunity: The Synergy of REGN3767 and REGN2810 in Humanized PD-1/LAG-3 Mice Models

The study investigates the potential of combining two monoclonal antibodies, REGN3767 and REGN2810, to enhance immune response against tumors. REGN3767 targets the LAG-3 receptor, which is known to suppress T-cell activity by binding to MHC II, while REGN2810 is designed to block the PD-1 receptor, preventing its interaction with ligands PD-L1 and PD-L2. Both receptors are implicated in immune evasion by tumors. Utilizing humanized mice models with human PD-1 and LAG-3 genes, the research demonstrates that the combined therapy of REGN2810 and REGN3767 significantly reduces tumor growth and extends survival rates compared to individual treatments.

Through RNA sequencing and RT PCR analysis, it was found that each monoclonal antibody induced substantial transcriptional changes within the tumor environment. The combination therapy led to an increase in immune activation signatures, suggesting a more potent immune response. The study identified T-cell expansion and activation as a result of the antibodies' action, with REGN3767 showing a delayed but comparable effect to REGN2810. Both treatments also activated other immune cells such as neutrophils, myeloid, and NK cells.

The combined use of REGN2810 and REGN3767 resulted in unique gene expression changes that were not observed with single treatments, indicating a synergistic effect. This combination also amplified the expression of checkpoint and costimulatory molecules like CTLA-4, CD40, and VISTA, which are crucial for immune response modulation. The findings support the advancement of REGN2810 and REGN3767 as a combined immunotherapy for cancer treatment, based on the robust immune activation observed in the preclinical study.