BisCCL2/5i is a novel single domain antibody that binds and neutralizes both murine CCL2 and CCL5. The dual blockade of CCL2 and CCL5 signaling with BisCCL2/5i leads to metabolic reprogramming of tumor-associated macrophages, providing enhanced therapeutic effect to treat liver malignancies when in combination with immune checkpoint blockade (ICB) therapy.
It has been known that tumor-associated macrophages (TAMs) compromise the efficacy of immune check point blockade (ICB) therapy in many types of solid tumors, including liver malignancies, in which CCL2 and CCL5 cooperatively induce the macrophage polarization toward M2 phenotype, prime immunosuppressive microenvironment, and render liver cancers resistant to ICB therapy.
University researchers have developed a novel affinity molecule BisCCL2/5i that has high binding affinity and specificity with murine CCL2 and CCL5, and the molecule is delivered in the modality of mRNA using clinically validated liver-targeted lipid nanoparticles. The consequential simultaneous deprivation of CCL2 and CCL5 is able to alter the intracellular metabolic processes of TAMs and switch their polarization status. The combination of BisCCL2/5i with ICB therapy produces a robust anti-cancer response in liver metastatic tumors.
· Bispecific targeting molecule, allowing for simultaneous CCL2 and CCL5 capture
Tumor microenvironment reprogramming, providing improvement of anti-PD-L1 immunotherapy for cancer treatment