Innovative Allogeneic CAR T Cell Therapy Trial Shows Promising Results

With a robust clinical trial program and state-of-the-art, in-house manufacturing capabilities, Houston Methodist Hospital is positioning itself at the forefront of the revolution in cellular therapeutics.

The latest advancement is allogeneic CAR T cell therapy, an innovative off-the-shelf immunotherapy derived from donor cells. Houston Methodist researchers are partnering with counterparts at other leading cancer institutes to pioneer this groundbreaking treatment, aimed at providing rapid access to immunotherapy for patients with limited options.

"In this era of increasingly precise, personalized and targeted therapies, speed has become an important differentiator," said Dr. Siddhartha Ganguly, chief of Hematology at the Houston Methodist Neal Cancer Center. "What good is it to have the world's best treatment if the patient dies or is too sick to benefit from it by the time it's ready?"

Promising early results

Houston Methodist has administered the novel treatment to seven patients as part of a first-of-its-kind, national, industry-sponsored Phase 1 clinical trial for patients with relapsed and refractory multiple myeloma. Early results indicate it is both safe and effective, especially for those who have exhausted conventional therapies.

At a recent Tandem Transplantation and Cellular Therapy Meeting, trial leaders announced an overall response rate of 86% among 35 enrolled patients, with no significant safety issues reported.

The findings are particularly noteworthy given the study population's challenging demographics: 53% of the trial participants were identified as having high-risk cytogenetics, 38% had extramedullary disease and 68% were previously exposed to a similar immunotherapy but failed to respond to the treatment.

Unlike traditional autologous CAR T therapy, which requires weeks-long personalized cell production, the allogeneic version utilizes pre-engineered, donor-derived T cells that can be immediately infused. This crucial advantage benefits patients with aggressive cancers.

"Many patients who qualify for CAR T therapy don't have the luxury of waiting four to six weeks for cell production," Dr. Ganguly said.

Cutting-edge gene-editing technology

Houston Methodist began its first allogeneic CAR T clinical trial in April 2024, treating a patient whose multiple myeloma was resistant to all standard therapies.

Employing CRISPR-Cas9 gene-editing technology, the therapy boosts the patient's immune response while removing immune rejection markers, demonstrating encouraging initial safety and efficacy results.

Of the seven patients who have undergone treatment at Houston Methodist to date, three achieved complete remission, while two experienced biochemical progression and required further treatment. Two more received the treatment too recently to analyze results.

Although Dr. Ganguly acknowledges the treatment is not a definitive cure, it has significantly improved disease control and survival in several cases.

"This is not a silver bullet, but it is an enormous step forward," Dr. Ganguly emphasized. "We are seeing extended remission periods in some patients and, importantly, have not observed graft-versus-host disease, a major concern with donor-derived therapies."

The treatment enhances therapeutic response by inserting an anti-cancer gene BCMA (B cell maturation antigen) and removing donor-specific antigens to prevent graft-versus-host disease. Additionally, the research team engineered a novel safety switch that can instantly eliminate infused cells if activated by specific medication.

"As far as we know, this is the first 'kill switch' of its kind to be introduced into a treatment like this," Dr. Ganguly explained. "It's incredible science fiction made real."

Expanding opportunities

Houston Methodist recently took a significant step toward autonomy in cell therapy manufacturing by opening the Johnson Center for Cellular Therapeutics, a FACT-accredited GMP lab enabling the hospital to produce its own CAR T-cell products.

"Previously, we depended on other institutions for cell processing," Dr. Ganguly noted. "Now, we have full control over manufacturing and storage, allowing us to expedite trials and expand treatment to other cancers."

Building on its successes in multiple myeloma, Houston Methodist is preparing clinical trials for other CAR T therapies targeting gastric and prostate cancers. The trial for gastric cancer is slated to begin this year, and the prostate cancer trials are planned for 2026.

Houston Methodist's contribution in allogeneic CAR T therapy is gaining global recognition. At recent international meetings, Dr. Ganguly presented promising data on the therapy's effectiveness against extramedullary disease — a particularly aggressive form of multiple myeloma that spreads beyond bone marrow.

Looking ahead, the hospital aims to enhance the durability of the therapy through maintenance strategies, including additional CAR T cell infusions over time.

"Our goal is continued improvement in persistence and efficacy," Dr. Ganguly said. "We're committed not just to treating myeloma but applying this technology broadly across various cancers."