7aaRGD

7aaRGD is a synthetic peptide designed to block SPP1 (secreted phosphoprotein 1, also known as osteopontin)/integrin signaling. It acts by targeting the interaction between SPP1 and αvβ3/αvβ5 integrins, which are implicated in the reprogramming of glioma-associated myeloid cells (GAMs) within the tumor microenvironment of glioblastoma (GBM). By inhibiting this pathway, 7aaRGD prevents the emergence of immunosuppressive GAMs and normalizes peritumoral blood vessels. While monotherapy with intratumorally delivered 7aaRGD does not reduce tumor growth in orthotopic gliomas, its combination with anti-PD-1 immune checkpoint inhibitors leads to reduced tumor growth, increased proliferation and activation of CD8+ T cells, depletion of regulatory T cells, and restoration of a pro-inflammatory ("hot") tumor microenvironment. This suggests that blocking SPP1/integrin signaling can overcome resistance to immune checkpoint inhibitors in GBM by modifying innate immunity and reinvigorating adaptive antitumor responses[1][4].