The Power of the Biomarker

Using T-Cell Clonality to Predict and Broaden Which Patients Will Respond to Checkpoint Blockade

Matt Coffey recently spoke about “the power of the biomarker” at the Annual General Meeting on May 2, 2019. Listen to the full webcast, and read an excerpt from his discussion here:

“Developing a biomarker eliminates the patients at baseline who aren’t going to derive benefit from treatment, resulting in a much smaller study that’s more likely to succeed. We can exclude patients who we know won’t benefit, never having enroll them. And this is the power of the biomarker: It allows us to immediately understand and recognize who’s going to respond to our treatment.

We’ve been examining T cell clonality as a predictive biomarker for a patient’s response to pelareorep in combination with checkpoint blockade. In our bodies, we have thousands and thousands of T cells—immune cells that linger, so that the next time you become sick, you have a faster response. T cells can also recognize tumors, some of which are clones: they know what the tumor once looked like, but through exhaustion, are no longer working properly. Treatment with checkpoint blockade causes these T-cell clone numbers to expand, driving a larger and larger population that can fight the tumor and retrain them to target disease.

But there is a problem: checkpoint blockade only works in one in five patients. If you don’t have this preexisting T-cell clone that recognizes the tumor, the blockade can’t—and won’t—do anything in patients.

Here’s where pelareorep comes in: The viruses are capable of fixing this problem. When you combine an oncolytic virus and the checkpoint blockade, you start to get the amplification of memory cells and CD8+ killer T cells. This destruction of the tumor will result in thousands of new T cells that can then activate against the tumor cells themselves. Thus, the combination causes event greater enhanced clonality, because it allows you to have both your preexisting T-cell clones, as well as an entirely new clone army to better target the disease.

In adding a virus to checkpoint blockade therapy, it allows us to reach a much broader patient population, because it doesn’t matter if these patients don’t have the existing T-cell clones at baseline—the virus makes them. It primes the immune system to work better, allowing it to make this enhanced T-cell clone army irrespective of the fact if the patient had them beforehand. These thousands of new clones—both expanded and brand new—are able to target and destruct the tumor.”