NRP1 antibodies disrupt its interactions with ligands such as VEGF, semaphorins, and SARS-CoV-2 Spike protein. Key mechanisms include:
Immune Modulation: Blocking NRP1 enhances CD8+ T cell cytotoxicity and reduces regulatory T cell (Treg) activity, reversing immune exhaustion in tumors .
Anti-Angiogenic Effects: Inhibition of VEGF/NRP1 signaling prevents vascular maturation, starving tumors of oxygen and nutrients .
Viral Entry Inhibition: Neutralizing NRP1-Spike interactions reduces SARS-CoV-2 infectivity .
CD8+ T Cell Reactivation: 53-IgG1 restored cytotoxicity in exhausted CD8+ T cells from NSCLC patients, increasing target cell apoptosis .
Co-Culture Experiments: Anti-NRP1 antibodies enhanced PBMC cytotoxicity against A549 cells, reducing tumor cell viability .
| Trial Phase | Antibody | Combination Therapy | Outcome | Source |
|---|---|---|---|---|
| Phase I | MNRP1685A | Bevacizumab | Stable disease in 7 patients; PlGF elevation |
NSCLC: 53-IgG1 demonstrated superior efficacy in humanized models, reducing tumor weight by 50% .
Combination Therapies: Anti-NRP1 + anti-PD-1 enhances CD8+ T cell infiltration and cytotoxicity .