ASCO 2026 | Intrathecal TRP1-targeted CAR T cell therapy in melanoma leptomeningeal disease

We are developing this new therapy for leptomeningeal disease, so let me just tell you what that is for a moment. It’s a rare complication of systemic cancer. We all know breast cancer, for example, goes to the lungs or liver or whatever. Sometimes it goes to the brain itself, but in this case it goes to the covering of the brain and it’s in the spinal fluid. So tumor cells go up there, they float all around in the brain and spine and they stick on stuff. And patients are really, really sick. Very, very bad prognosis, maybe two or three or four months at the most. So it’s a huge unmet medical need. And then we think it’s becoming more common. There’s something about the spinal fluid in the brain that tumor cells like. It’s like a sanctuary site. They just like to sit there and grow. In any event, we had a couple of approaches to this. One is my colleague, Dr. Jose Guevara, developed this. He built a new CAR-T, which is directed against this protein that’s expressed on melanoma cells called TRP1, which doesn’t matter. But a CAR-T is basically using your own T cells, and then you put on a receptor for your protein of choice, and it’s like a homing device. So it’s like a smart bomb or something. So in this case, the smart bomb is meant to explode on TRP1. And in mice, we administer this directly into the spinal fluid, and it looks like it cures most of the mice, which is pretty unbelievable. Here’s this melanoma line that’s really aggressive, V16, that all the mice usually die within two weeks at the most. Some of the mice are living for like two or three months. So it’s good to do that. But we’re in the business of trying to help patients. Next, I had to determine if this is expressed in people in leptomeningeal disease. So it is expressed on the surface of the melanoma when it goes on the surface of the brain. And it’s expressed on the cell surface. So it’s not just in the middle of the cell where it’s not accessible. It’s on the outside where your T cells can get it and attack it and kill it. So it looks pretty promising. We also found that if you’re cured using this, that when you try to give mice leptomeningeal disease again, they’re kind of resistant to it, which is something good for patients because almost everybody with cancer would go through a lot if they could just, once it’s done, it’s cured and they’re done, right? So that’s kind of prevention. And prevention is another thing that we’re doing. So it’s truly to tell about patients, but we’re developing this and going through the production of the CAR-T and all that stuff so that we can get an infusion. It’ll probably take a couple of years. So it’s kind of promising. It’s exciting to be at Moffitt and work with people like Dr. Guevara because we work as a team. I’m like a physician scientist or clinical staff, lab staff, immunology, bioengineering, mathematics, AI, trying to bring all these disciplines together to focus on cancer. So it’s kind of exciting. I hope it works.

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