In this segment, Carlen A. Yuen, MD, a specialist in the field of neuro-oncology, shares a case study of a 40-year-old patient with recurrent grade 4 IDH-mutant astrocytoma. After failing standard-of-care treatments, the patient was offered a novel immunotherapy approach using bispecific T-cell engagers (BiTE therapy), targeting a tumor-specific DLL3 marker.
Yuen illustrates the rationale behind next-generation immunotherapies — including PD-1 inhibitors, CAR T cells, and BiTEs — and how these agents are helping turn “cold” tumors into immune-responsive environments.
This case reflects the power of precision oncology, collaborative care at UCI Health and the UCI Health Chao Family Comprehensive Cancer Center, and the evolving landscape of immunotherapy in CNS tumors.
Now we'll move on to a second case. This is a case another patient of mine, of a 40-year-old male with a recurrent grade 4 IDH mutant astrocytoma. He was treated at an outside hospital with a gross total resection. He underwent radiation and chemotherapy, that standard of care, and then he developed this mass here. He presented to our hospital and because this tumor was local, it was resectable. Doctor Chen was able to near totally resect this, and you can see that here. There's some residual here at the borders, and he has some residual disease in other areas as well. Now what to treat him with? He already failed standard of care. I could give him chemotherapy, but he's only 40 years old and he hopefully has a long time to live. So let's look to other novel options. We know that immunotherapy has revolutionized cancer care for other solid tumors. This is the first time that we can use the word cure and cancer in the same sentence, and the work of Doctor Allison and Doctor Hanjo led to the 2018 Nobel Prize in Medicine for them. For their work. Now, immunotherapy for CNS tumors has not seen the same success. Here's some of the research that I've done that I wanted to share, using immunotherapy for brain tumors and also for liquid tumors with metastatic spread to the CNS. We also know that these immunotherapies can cause autoimmune disease, because what you're basically doing is you're taking the breaks off your immune system and you're unleashing your immune system, so it's hyperactive and you can develop some autoimmune disease like Guillain-Barre, um, or facial palsies or something called ICANs with CA T cell therapies. To understand how these work, we have to understand how does our immune system work? Well, it's kind of like the TSA. The TSA agents are your T cells, and you're going through the airport, you're going through security, and what your T cells are supposed to do is survey every cell that goes by. If there's an infected cell, it's supposed to eliminate it. If there's a cancer cell, it's supposed to eradicate it. But sometimes these tumor cells, they wear a disguise and they bypass security. And that disguise can take the form of PDL1 ligands. So here's a tumor cell here. It expresses these ligands, PDL1 and PDL-2. It binds to the PD1 receptor on the T cell, and basically it's telling it, suppress, don't kill me, I'm a normal cell. But what if you use immunotherapy and you block that message? Then you're unleashing your immune system to allow it to do its job, and this is how PD one inhibitors work. That's just one way. We also have CAR T cells, chimeric antigen receptor T cells that works very well and is FDA approved for a number of hematologic malignancies. Here is a blue glioma cell here in a mouse model. The white cells are dendritic cells that are supposed to find and locate the tumor cells. The red cells are T cells that are surveying the environment, but I don't think they're doing much of a good job right there cause they haven't located the glioma cell yet. Now here on the right you can see the dendritic cell has identified that this is a foreign cell. It's alerted the T cells, and now the T cells are honing in for the attack. We also have light therapy by specific T cell engagers, and this is what our patient is being treated with. His tumor specifically has this DLL3 marker, so he is being given a drug that is a linker molecule that links to his tumor cell. And then links to his T cell and brings them together. And this allows his immune system to proliferate. It can lice the tumor cells that will release all the antigens and release all the cytokines, and that will turn this cold tumor into an inflamed hot immune rich tumor that can do its job. And here you could see after 6 months, all the white here is enhancing disease has now started to resolve.
