The Influence of Targeting CCR5 Receptors

In conversation with Pharmaceutical Executive, Dr. Jay Lalezari, CEO, CytoDyn, outlined how the CCR5 receptor has emerged as a critical target in the fight against metastatic cancer. Lalezari explained CCR5 functions and also highlighted the role of regulatory T cells, or Tregs, as another CCR5-positive cell type that cancers exploit. Below a transcript of the conversation between Pharmaceutical Executive and Dr. Lalezari can be found.

Pharmaceutical Executive: Can you explain how targeting the CCR5 receptor influences tumor progression and why it’s emerging as a key target in metastatic cancers?
Dr. Jay Lalezari: Over the years, it became clear that actually CCR five is there for many reasons besides letting the virus in, and that it actually plays a key role in solid tumor oncology. And there are a number of proposed ways in which CCR five helps solid tumors, both in the spread and migration of cancerous cells, which is important because it's generally not the primary tumor but the metastasis that that kill patients. So CCR five is there as a GPS system to help cells navigate and migrate to where they're needed, particularly in an inflammatory response, and cancer can co-opt that system to then help their cells spread throughout the body. Also, CCR five plays a role in creating a tumor microenvironment that protects the cancer. So, when a solid tumor, be it colon or breast or pancreas or prostate, wants to start growing one way, there are two things that it has to do. One is it has to attract and build a blood supply that allows it to grow beyond, I think, two millimeters. The other thing is it has to do is that it is a foreign antigen, and so it has to figure out a way to keep the immune system from attacking it. And there are a lot of ways in which cancer can do that. I'm not an oncologist. I can't list them all, but one way cancer solid tumors do it, is by using signaling through CCR five and macrophages or CCR five positive, and when the tumor secretes the chemokine, we call it RANTES or CCL five, when it binds to the receptor on macrophages, they switch their allegiance from cells that would be attacking the cancer to cells that Now promote the tumor's growth and in part by secreting factors, VEGF being one of them that help build the blood vessels the cancer needs to bring nutrients to the growing tumor.