Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors

Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.

Through computational techniques, we generated highly potent mutated CD84 mini-proteins and peptides as antagonists with significantly higher affinity for CD84 to mimic the key features of the IgV-like domain of the protein. Additionally, we engineered an antibody capable of blocking CD84. Binding affinities were assessed using dissociation constant (Kd) calculations.

Data analysis shows that the Kd values for the designed peptides ranged from 10 to 100 times stronger than those of the natural CD84 interactions, indicating efficient inhibition of CD84 interactions. Additionally, mutagenesis of the Ig-like V domain of CD84 resulted in variants with improved binding stability, with a Gibbs free energy change (ΔΔG) indicating enhanced interaction potential.

This study provides insights into CD84 interactions and their implications for immunotherapy targeting MDSCs in solid tumors. However, experimental validation is necessary to confirm the findings of this study and evaluate peptide selectivity as potential molecular therapeutics.