Researchers in Japan have demonstrated a new antibody treatment for prostate cancer. The drug helps reverse a nasty trick that cancer cells play on the immune system, with promising results shown in experiments in dogs with the cancer.
Cancer uses a range of devious tricks to hide from the immune system, including turning some of its own cells against it. Regulatory T cells (Tregs) have an important role in tagging the body’s own cells as “self” so the immune system doesn’t mistakenly attack them, as happens in autoimmune diseases. But cancer cells seem to be able to hijack this mechanism, tricking Tregs into marking them as "self" and preventing other immune cells from attacking, allowing the disease to grow and spread.
High levels of Tregs have been detected in several types of cancer, so one emerging treatment is to administer antibodies that reduce levels of Tregs in the area. For the new study, scientists from the University of Tokyo investigated this technique in dogs, which have a prostate with a similar structure to that in humans. These dogs were pets that had naturally occurring prostate cancer.
First, the team analyzed the degree to which the prostate cancer had been infiltrated by Tregs, and how that happens. Using RNA sequencing and protein analysis, the researchers found that Tregs seem to be attracted to the tumor in higher amounts when a protein called CCL17 binds to a receptor called CCR4.
Next, the researchers administered an antibody drug called mogamulizumab, which blocks the CCR4 receptor. The dogs that received the drug were found to have lower levels of Tregs circulating and survived longer, with few adverse side effects.
While it’s still early days for the treatment, the team says there are promising signs that the results could carry across to humans. Analyses on human prostate cancer patients revealed that they also had high levels of tumor-infiltrating Tregs expressing CCR4. And mogamulizumab has already been approved for use in humans by the FDA and similar agencies in other countries, as a possible treatment for a range of other diseases.
The research was published in the Journal for Immunotherapy of Cancer.
Source: University of Tokyo
