Cell therapy clinical trial could bring hope for patients with T-cell lymphoma and beyond

During his medical residency, Sattva Neelapu, M.D., felt the pull of oncology. He was drawn to the opportunity to make a real difference in patients’ lives. He was motivated by the challenge of treating such aggressive diseases.

But he couldn’t help noticing that chemotherapy, radiation and surgery all had limitations. And he hated seeing his patients suffer from the side effects that came with these standard pillars of cancer treatment.

Research offered him the chance to give them more. So, he became a physician-scientist, conducting translational research, the branch of science in which lab discoveries are transformed into real-life medical treatments.

Neelapu became a lymphoma and myeloma specialist, focusing on B cell and T cell lymphomas and other malignancies that start in these critical immune cells. Eventually, he came to UT MD Anderson, where he works today.

He gravitated toward the latest development and became interested in immunotherapy, as it provided an opportunity to specifically target cancer cells without damaging normal tissues, and later, cell therapy, one of the leading frontiers in cancer treatment, in which living immune cells are engineered to attack cancer in a highly personalized process.

Now, through his latest clinical trials, Neelapu is on the cusp of extending the reach of CAR T cell therapy, a treatment that, if successful, could be used to treat certain subtypes of T cell lymphoma or even some autoimmune disorders.

Finding hope for T cell lymphoma patients in CAR T cell therapy

Neelapu recently launched a Phase 1 study on a potential new treatment using CAR T cell therapy for patients with T/NK cell lymphoma that has relapsed.

The study’s goal is to test a CAR T cell therapy derived from the patient, potentially bringing new treatments to more T and NK cell lymphoma patients.

T cell lymphoma includes several rare forms of non-Hodgkin lymphoma, a blood cancer. These cancers begin in the T cells, a type of white blood cells, and are often found in the lymph nodes or spleen, but may also be found in other places.

NK cell lymphoma is another rare type of cancer that develops from the Epstein-Barr virus. This very misunderstood cancer type appears in natural killer T cells in the nose and sinuses.

Many T cell lymphomas recur, even after patients enter remission. So, researchers are constantly looking for new treatments so that T cell lymphoma patients can live longer lives. Researchers hoped that CAR T cells would be that treatment. CAR T cell therapies have been transformative for patients with refractory B- cell leukemias and lymphomas, as well as multiple myeloma.

This highly personalized medicine, which relies on a patient’s own cells after genetically engineering them to attack cancer, hasn’t been very successful in treating T cell lymphomas. And so far, no approved CAR T cell therapies exist for this cancer type. That’s because CAR T cell therapy is dependent on T cells, and in T cell lymphoma, that’s where the cancer is.

When the healthy T cells enter the patient (typically through an IV), both the healthy T cells and the cancerous T cells start attacking each other. In other cases, the treatment kills all the T cells. In both instances, the treatment fails.

A new treatment approach using CAR T cell therapy

Neelapu has a new approach. He’s testing a specific kind of CAR T cell therapy: JV-394 anti-CD-94 CAR T cell therapy. In this treatment, the therapy is engineered to target a specific protein, CD94.

CD94 is found on the surface of nearly two-thirds of natural killer cells and some T cells. It plays a role in controlling how the immune cells behave and determines whether they should become more aggressive as they attack viruses or tumor cells or if they should calm down.

Through previous research, Neelapu could see that some types of leukemia and lymphoma that come from NK cells or T cells have unusually high levels of CD94. Research also showed that CAR T cells engineered to target CD94 had the potential to be highly effective at killing these CD94 positive cancers.

If this treatment is successful, it would be the first in-human proof that CD94 can be safely and effectively targeted in cancer with CAR T cell therapy, opening up a whole new antigen space for these cancer types. On top of that, it could provide a new foundational therapy or a bridge to a transplant for many patients who have cancers that have been very difficult to treat.

“It’s incredibly rewarding to see our work move from the lab into medical care, where it can truly help patients and push the field forward much faster,” Neelapu says. “I look forward to seeing what breakthroughs we can drive for our patients.”

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