Cancer immunotherapy may also treat autoimmune diseases

A team of researchers has found disrupting the interaction between cancer cells and certain immune cells is more effective at killing cancer cells than current immunotherapy treatments.

The findings, which include studies in cell lines and animal models, appeared in JCI Insight and focus on a protein called CD6 as a target for a new approach to immunotherapy.

Over the past two decades, new approaches to cancer treatment have been developed that block immune checkpoints, which are receptors on the surface of certain immune cells, like natural killer T cells. Cancer exploits these immune cells and renders them dormant.

This treatment, called checkpoint inhibitor immunotherapy, gives these immune cells a chance to fight back. Unfortunately, patients that become cancer-free are often left with autoimmune conditions that can become fatal. Only approximately one third of patients with cancer ultimately benefit from currently available immune checkpoint inhibitors.

David Fox, a rheumatologist and cancer researcher at the University of Michigan Rogel Cancer Center, said: “I’m interested in how cancer cells interact with certain immune cells to control the immune response to cancer, and how the immune system interacts with organs and tissues to cause autoimmune diseases”.

This new study proved successful in combatting human breast cancer, lung cancer and prostate cancer in cell lines, indicating that the anti-CD6 antibody, known as UMCD6, could be useful in treating a wide range of cancer types.

The researchers also grafted human breast cancer cells into immunocompromised mice and followed up with transferring human immune cells into the mice. When given an injection of UMCD6, the tumours were almost entirely eradicated in a week, compared to mice treated without UMCD6. CD6 has been known to play a role in autoimmunity, since mice that don’t have CD6 on their immune cells have major suppression of autoimmune diseases.

Prior research has shown that an antibody that binds to CD6 and pulls it from the cell surface to the inside of the cell can effectively treat autoimmune mouse models of three different human diseases: rheumatoid arthritis, multiple sclerosis, and uveitis. Now, when treated with UMCD6, Fox saw the mice show striking reductions in disease activity, autoimmunity and organ damage in mice.

“When UMCD6 binds to CD6 on these specific immune cells, it creates a CD6 cluster that dives into the interior of the cell, allowing no CD6 to remain on the cell surface” says Fox. “This causes the killer T cells to seek out and destroy the cancer cells much more aggressively. At the same time, removing CD6 from the surface of CD4 cells, with the same UMCD6 antibody, controls and limits the activity of the CD4 cells, which are the cells that instigate autoimmune diseases.”

There are ongoing studies of anti-CD6 antibodies in India, where an anti-CD6 antibody has been approved for the treatment of psoriasis. However, in the United States, substantial research remains to be done to translate the discovery from laboratory models to human clinical trials.

 

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