While the focus and promise of CAR T-cell therapies has long been on liquid tumors and hematologic malignancies, new trials under way at Roswell Park Comprehensive Cancer Center are expanding the applications of immunotherapy to include other diseases.
“We have a couple different CARs in development for things like MS, rheumatoid arthritis, even Sjögren’s syndrome and lupus,” says Brian Betts, MD, Vice Chair of Strategic Initiatives for Transplant and Cellular Therapy at Roswell Park. Early indications find that CAR T-cells “cause better eradication of the B cells responsible for autoreactivity.”
Another trial, for what is likely to be an armored CAR T-cell treatment, will be for DLL3, a cell that “secretes its own cytokine,” Dr. Betts says. “That helps the CAR T cell persist, hang around in the microenvironment longer and makes it able to kill better too.” This is being studied for patients with small-cell lung cancer as a possible way to help reduce their repeated exposure to chemotherapy.
Hi, I'm Brian Betts. I'm one of the vice chairs here at, uh, Roswell Park Comprehensive Cancer Center. I specialize in transplantation and cellular therapy, and we'll be talking mostly today about CAR T cells and how that might relate to cancer, as well as, um, other non-cancer applications too like autoimmunity. There's several pretty important clinical trials that we'll be talking about. Not all for hematologic malignancies. Actually, some of them are even for solid tumors and not even for cancer at all. The first trial I wanna talk to you about is coming out of Marco Davila's lab, anti CD-19, CD20 BB mute. which means it's targeting two different antigens, CD-19 and CD20. While you might think of that as being an anti-cancer CAR T cell, we're actually going to be applying it towards autoimmunity. As it turns out, malignant B cells overlap a lot with the B cells that cause autoimmunity. And there's actually a couple of different cars that are in clinical trials right now for things like MS, uh, rheumatoid arthritis, and even Sjogren's syndrome and lupus. We're trying to go after multiple targets on the B cells to cause better B cell eplasia to actually eradicate the B cell that's responsible for auto reactivity, and we think that'll be more effective in helping these patients and ultimately potentially curing them as well. One of the benefits of the new 1920 BB 6 CAR T cell and how we're going to be using it in autoimmunity, the goal there is not only to help patients and ultimately eradicate disease, but also to limit exposure to long-standing immune suppression or modifying drugs, which could have a direct impact on quality of life and even disease control as well. The other cell I want to talk to you about is coming out. Of Vernier Brenn's lab. It's targeting DLL 3, which will likely be armored. That basically means it's a CAT cell that secretes its own cytokines. It's kind of like a BYOC, bring your own cytokine to the party. Why is that important? Well, it helps the CAR T cell persist or hang around in the microenviron longer and actually makes it able to kill better too. This particular cell, DL3. is going to be going against small cell lung cancer, so we're kind of moving out of the hemologic malignancy space like lymphomas and acute lymphoblastic leukemia and moving into solid tumors, um, in particular lung cancer or small cell lung cancer. A lot of these patients have seen prior chemotherapy. Small cell lung cancer is one of those we actually use a lot of chemo radiation as well. So having a cell that could potentially free them up from, you know. Recurrent exposure to chemotherapy could actually be beneficial in and of itself. When we think of Roswell Park, you kind of think of, oh, it's a place where we treat cancer, which is true. We do that, we do that very well. But we're actually bringing together other disciplines, especially in uh transplant and cellotherapy. We have dedicated specialists in rheumatoid arthritis and, and autoimmunity, as well as chronic graft versus host disease, which we'll be overseeing. A lot of aspects of these trials, especially with the uh CD 1920 BBM 6 trial. Also with the DLL 3, we have, it's a unified approach between transplanted cellular therapy, our colleagues and friends over at Solid Tumor and thoracic. So we have every specialist you need all in one house, and we're happy to collaborate with providers outside of the center as well. The, the goal is to, you know. Help your patients, get them on the right track after receiving cell therapy and then hand them back to you and do this all as a team.
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