Chimeric antigen receptor (CAR) T-cell therapy has changed the outlook for some of the hardest-to-treat blood cancers. This highly engineered form of immunotherapy can produce deep, lasting remissions for patients whose disease has returned despite multiple treatments.

But even as one of cancer medicine’s most advanced therapies, MCW Cancer Center researchers are asking how it can be made better.

Across several clinical trials, investigators are tackling the limitations that still stand between CAR T-cell therapy and more patients, including the time it takes to produce each treatment, how long engineered cells remain effective, and cancer’s ability to change and escape them.

“These advances offer something particularly important to patients whose blood cancer has returned or stopped responding to treatment: another opportunity when conventional treatments are no longer working,” said Binod Dhakal, MD, MS, Professor of Medicine. “The long-term goal is to move beyond repeatedly controlling disease and toward longer-lasting, potentially treatment-free remissions for many more patients.”

These efforts are being recognized on a global scale. This summer, promising findings from trials led or advanced by MCW investigators were presented at the European Hematology Association (EHA) Congress in Stockholm, Sweden. Together, they reflect a mindset driving cancer research at MCW: being at the cutting edge means asking what lies beyond it.

An Advanced Cancer Therapy, Made Better

Most CAR T-cell therapies are made by collecting a patient’s T cells, engineering them in a laboratory to recognize cancer, and returning them to the patient ready to attack it. The approach can be remarkably effective, but creating a personalized therapy takes time that patients with fast-moving cancers may not have.

“Many patients experience disease progression while waiting several weeks for their treatment to be manufactured. An off-the-shelf CAR-T product could potentially be available much more rapidly, allowing treatment when patients need it most,” said Mehdi Hamadani, MD, Professor of Medicine and Chief of Hematologic Malignancies.

Dr. Hamadani is testing that possibility in the phase 1 ANTLER trial. The Caribou Biosciences study evaluates vispa-cel, an investigational therapy made in advance from healthy donor T cells for patients with B-cell lymphoma. The cells are edited using CRISPR technology to reduce complications from donor cells and help them fight cancer longer.

Results presented at EHA were encouraging. Among 22 patients, 82% responded, 64% achieved a complete response, and 51% were alive without their disease progressing one year later. If successful in larger studies, the approach could point to a future where CAR T-cell therapy does not have to be built from scratch for every patient.

Dr. Dhakal is exploring how far the off-the-shelf concept can go in the CaMMouflage trial for multiple myeloma (MM). The phase 1 study is evaluating CB-011, another therapy made from healthy donor T cells, with “immune-cloaking” edits designed to help them avoid rejection by the patient’s immune system. The cells are engineered to recognize BCMA, a protein found on myeloma cells.

Findings shared at EHA showed that 92% of patients who had not previously received a BCMA-targeted therapy responded, and 83% achieved a complete response or better. Half remained in complete response or better at 15 months.

“What is particularly important is the concept rather than simply the response rate,” Dr. Dhakal explained. The study shows what may be possible when CAR T cells are engineered not only to attack cancer, but to overcome biological barriers that can limit how well they work.

But getting better cells to patients is only part of the challenge. Sometimes, cancer finds ways to escape them.

That problem has driven years of research by Nirav Shah, MD, MS, Professor of Medicine and Medical Director of the Cancer Center Cell Therapy Shared Resource. Rather than engineering CAR T cells to recognize one target, his approach goes after two, CD19 and CD20, giving them a second way to recognize chronic lymphocytic leukemia (CLL) if one is lost.

New findings presented at EHA showed how the strategy is progressing in Dr. Shah’s ongoing LV20.19 trial. Among 18 patients, 89% responded and 78% achieved a complete response or complete response with incomplete blood count recovery. Researchers also found that lowering the dose maintained responses while reducing serious side effects.
“Cancer is very good at finding ways around treatment, which is why we’ve spent years developing an approach that gives CAR T cells more than one way to find it,” said Dr. Shah. “We want to keep learning from our patients and use those lessons to make these therapies better and safer.”

Pushing Limits in the New Cell Therapy Lab

Soon, MCW investigators will have a dedicated space to push these boundaries even further.

This September, the Cancer Center will officially open its new Cell Therapy Lab in the Medical College of Wisconsin Michels Center for Cancer Discovery. Expected to be fully operational by the end of 2026, the lab will expand opportunities for researchers across the institution to manufacture and test cellular therapies on site.

With greater capacity and improved technology, research teams will be able to move more quickly between what they learn in the lab and from patients, accelerating the development of new and better treatments.

“Our goal should be not simply to bring existing cellular therapies to Wisconsin,” said Dr. Dhakal, “but to develop the next generation of those therapies here.”