ONCOLOGY

Leronlimab’s Mechanism of Action for Immuno-oncology
Read More on CCR5

Upon malignant transformation, pathological expression of CCR5 occurs in many types of cancer.

In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness.¹ CCR5 expression induced by transformation imbues the cell with dramatic alteration in motility, gene expression, and homing behavior to metastatic sites.² CCR5 augments the pro-inflammatory pro-metastatic immune phenotype and enhances DNA repair, providing aberrant cell survival and resistance to DNA damaging agents.²

It is believed that CCR5 may play an integral role in tumor progression in a variety of cancers. CCR5 is overexpressed in breast cancer, prostate cancer, colorectal carcinoma, melanoma, head and neck cancer, gastric cancer, esophageal cancer, pancreatic cancer, and other tumors.¹Increased CCR5 expression is an indicator of disease status in several cancers.

Leronlimab’s Potential

• Research has shown multiple key properties of the CCR5’s role in cancer:
  • The CCR5 receptor on cancer cells potentially plays a role in the migration and invasion of cells into the bloodstream, which may lead to metastasis of breast, prostate, and colon cancer.
  • Blocking the CCR5 receptor on Tregs also turns on anti-tumor fighting properties restoring immune function.
  • Blockage of the CCR5/CCL5 interaction had a synergistic effect with chemotherapy and controlled cancer progression.
    • Chemotherapy traditionally increased expression of CCR5, so blocking CCR5 is expected to reduce the levels of invasion and metastasis.
  • Animal studies revealed a significant decrease in angiogenesis following administration of leronlimab.
  • The CCR5 receptor has been shown to play an integral role in macrophage repolarization due to macrophage plasticity.

¹Velasco-Velázquez M, Jiao X, De La Fuente M, Pestell TG, Ertel A, Lisanti MP, Pestell RG. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res. 2012 Aug 1;72(15):3839-50. doi: 10.1158/0008-5472.CAN-11-3917. Epub 2012 May 25. PMID: 22637726.

²Jiao X, Nawab O, Patel T, Kossenkov AV, Halama N, Jaeger D, Pestell RG. Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology. Cancer Res. 2019 Oct 1;79(19):4801-4807. doi: 10.1158/0008-5472.CAN-19-1167. Epub 2019 Jul 10. PMID: 31292161; PMCID: PMC6810651