CAR T Being Explored in Glioma Following Successes in Blood Cancer

After making strides in the treatment of blood cancers, innovative CAR-T cell therapies are now being explored for the treatment of solid tumors such as gliomas, an expert explained in an interview with CURE.

“We initiated trials where we introduced CAR-Ts into the brain for brain tumors, specifically for high-risk gliomas, diffuse midline gliomas and diffuse intrinsic pontine gliomas, and we learned that we were getting very nice responses, but we couldn't just give the CAR-T once, like we do for blood cancers. We had to give repeated doses of the CAR-T to sustain the response we were seeing,” explained Dr. Tanja A. Gruber.

Gruber, division chief of Pediatric Hematology, Oncology, Stem Cell Transplantation & Regenerative Medicine at Stanford Medicine Children's Health, spoke with CURE about the impact of CAR-T cell therapy and what is next for the transformative therapy.

Transcript

How has CAR-T cell therapy impacted pediatric patients with blood cancers and solid tumors?

In terms of blood cancers, what was truly amazing is that CAR-T therapy was able to put patients into remission who were very resistant to chemotherapy. We were able to cure children that chemotherapy couldn't, which was a huge advance in our field. The other thing we learned is that some of the factors that might make a patient resistant to chemotherapy don't necessarily make them resistant to CAR-T. That's because CAR-T therapy is a very different way of killing cancer cells; it involves engineering a patient's own immune cells to recognize and kill the cancer, which is very different from how chemotherapy works, which targets rapidly dividing cells.

We would, of course, anticipate a similar response with CAR-T cells for brain tumors or solid tumors. While we have seen some very encouraging responses, it wasn't the immediate home run we saw for blood cancers. This is because brain tumors and solid tumors are very different from blood cancers. A blood cancer circulates all over the body and is a cancer of immune cells.

With solid tumors, you have what we call a microenvironment, meaning the tumor is located somewhere in your tissues as a mass, and there are a lot of immune cells present within that tumor. So, the CAR-T cells don't just have to recognize and kill the tumor; they also have to get around that microenvironment, which can sometimes create barriers that prevent a response.

Here at Stanford, we've learned a lot about CAR-T cells. We initiated trials where we introduced CAR-Ts into the brain for brain tumors, specifically for high-risk gliomas, diffuse midline gliomas, and diffuse intrinsic pontine gliomas. We learned that we were getting very nice responses, but we couldn't just give the CAR-T once, like we do for blood cancers. We had to give repeated doses of the CAR-T to sustain the response we were seeing, and that's because of the microenvironment. So, I think moving forward, the research is really going to be about asking, “How do we break down that barrier, or that resistance, to be able to give a CAR-T just once, for example?”

Transcript has been edited for clarity and conciseness.

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