Off-the-Shelf CAR T-Cell Therapy Evaluates Survival in Relapsed T-ALL/LBL

Off-the-Shelf CAR T-Cell Therapy Evaluates Survival in Relapsed T-ALL/LBL

The T-RRex trial is evaluating Sofi-cel, an innovative allogenic CAR T-cell therapy for patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Sofi-cel (WU-CART-007) has received Breakthrough Designation from the FDA.

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Key Takeaways

Relapsed/refractory T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma are unmet clinical needs with few effective therapies.
Clinical trial for Sofi-cel, a novel therapy, evaluates the potential to achieve remission, and accelerate time to transplant to prolong survival.
Optimal referral timing is at first relapse, prior to additional chemotherapy that may elevate infection risk.
Trial enrollment is available for patients from 6 months to 39 years old with relapsed or refractory disease.
Cincinnati Children’s provides coordinated CAR T-cell therapy and transplant oversight, enabling comprehensive management during the clinical trial.

Novel CAR T-Cell Therapy Targets Gap in Care for T-Cell Cancer

T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL) are rare cancers that typically affect pediatric and young adult patients. These diseases are aggressive and fast-growing, but for many children, initial treatment can lead to a cure. Relapsed or refractory disease, on the other hand, is more challenging to treat.

Clinicians and researchers at Cincinnati Children’s are part of an effort to improve treatment options for patients who struggle with lingering T-ALL and T-LBL. In an active clinical trial, investigators will test a novel chimeric antigen receptor (CAR) T-cell therapy called Sofi-cel. It’s a modified CAR T-cell treatment that’s designed to induce remission, prepare patients for stem cell transplant and potentially improve long-term outcomes.

“Compared to B-cell ALL or LBL, T-cell disease at relapse is significantly harder to treat,” says Jeremy Rubinstein, MD, PhD, the pediatric oncologist leading the clinical trial at Cincinnati Children’s. “With WU-CART-007, Sofi-cel, we saw positive results from a first-in-human study. We are pleased to actively recruit patients to the now registrational T-RRex study. Our hope is to get patients with recurring disease to remission for stem cell transplant.”

Trial enrollment is open and ongoing.

Facing T-ALL Treatment Hurdles

“A bone marrow transplant is the gold standard for curing all patients with T-ALL and T-LBL,” Rubinstein says, “but patients must be in a deep remission beforehand for transplant to be a feasible option.” Successful chemotherapy is vital to achieving that goal. But patients with persistent T-cell cancers frequently resist the treatment, with only 20% to 40% responding to salvage chemotherapy.

“One big problem is that these patients are often chemotherapy-insensitive at relapse. They relapse early either while they’re still getting upfront chemotherapy or shortly after,” he says. “So, we see they often have proliferative disease that is highly resistant.”

As a result, historically many children have been unable to achieve a remission following relapse of their disease.

The nature of CAR T-cell therapy has also been an obstacle. The therapeutic cells, created to target diseased T-cells, inadvertently attack and kill other CAR T cells. This complication renders the treatment ineffective.

Sofi-cel’s developers deleted CD7 from the CAR T cell itself. This way, the CAR T cells don’t kill each other. Patients are better able to achieve remission and move toward a stem cell transplant.

Jeremy Rubinstein, MD, PhD

In the last decade, CAR T-cell therapy has revolutionized relapse care for B-cell ALL. However, there have been several barriers to achieving the same level of success for T-cell disease. This clinical trial is testing a product that has been engineered to overcome those hurdles.

Jeremy Rubinstein, MD, PhD

Sofi-cel Meets Clinical Need: Addressing Resistant Disease

According to Rubinstein, Sofi-cel could be an important step to long-term survival. This therapy, developed by Wugen, a U.S. cellular therapy company, is a genetically engineered product that supports remission of T-cell disease. And, as an allogenic, off-the-shelf therapy, it eliminates the need to manufacture autologous CAR T cells, allowing for a quick transition to starting the therapy. Consequently, it can accelerate the time to potentially curative stem cell transplant.

Through CRISPR-Cas9 editing, Sofi-cel overcomes the challenges posed by T-ALL. Over 95% of patients with T-ALL and T-LBL have disease expressing the T-cell antigen CD7. However, in Sofi-cel, CD7 is absent.

“Sofi-cel’s developers deleted CD7 from the CAR T cell itself,” Rubinstein says. “This way, the therapeutic T cells don’t kill themselves. Patients are better able to achieve remission and move toward stem cell transplant.”

Sofi-cel’s genetic modifications also sidestep the risk of graft-versus-host disease (GVHD) that often accompanies allogeneic therapies. CRISPR editing also deleted the T-cell receptor alpha constant gene that allows T cells to recognize and reject foreign proteins.

To date, a Phase 1 study with 28 patients with T-ALL or T-LBL disease has revealed encouraging results. Published in Blood, the trial demonstrated that over 90% of patients who received WU-CART-007 (Sofi-cel) responded positively to the treatment. Roughly 73% achieved complete remission, and eight patients underwent stem cell transplant.

Delivering Sofi-cel: Advancing Care Close to Home

To increase access to this potentially life-saving innovation, Cincinnati Children’s is part of a multi-center trial that brings Sofi-cel closer to home for T-ALL and T-LBL patients. The trial is open to children 6 months and older with:

First relapse
No active infections
Refractory disease after upfront therapy
Three or fewer previous treatment lines

Investigators plan to enroll up to 80 participants. Referring physicians should inquire about enrolling patients at the first sign of recurrent or refractory disease, Rubinstein says. Cincinnati Children’s can treat patients up to 39 years old for this study.

“I recommend providers consider referring patients at the time of relapse before starting additional chemotherapy that could increase infection risk,” he says. “Because Sofi-cel is an off-the-shelf product, reaching out as soon as possible so we can evaluate the patient saves valuable time.”

During treatment, Rubinstein’s team will assess patients’ progress. They will also monitor patients for cytokine release syndrome, neurotoxicity, and the potentially life-threatening inflammatory condition known as immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS).

Collaborative, Integrated Approach Supports Delivery of Care

For this trial, Cincinnati Children’s is one of a handful of clinical sites, including Children’s Hospital Los Angeles, Children’s Hospital of Philadelphia, City of Hope, MD Anderson Cancer Center and Seattle Children’s Hospital. Of this group, Cincinnati Children’s is uniquely positioned to deliver Sofi-cel and evaluate its efficacy, Rubinstein says.

“Our patients need both oncologic and cellular therapy care during their treatment course. In our CAR T team, there’s a very strong partnership between our oncologists and bone marrow transplant physicians,” he says. “We work closely together to deliver targeted care to these patients.”

The health system’s CAR T team also includes other physicians and nurse practitioners who have expertise in treating and managing T-ALL. Together, they help patients navigate traditional and novel treatments.

“We’re one of the very few health systems able to take a unified, integrated approach to treatment,” Rubinstein says.

To learn more about the trial or to refer a patient, contact Jeremy Rubinstein, MD, PhD.

(Published February 2026)

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