A novel form of immunotherapy aimed at aggressive blood malignancies demonstrates encouraging outcomes along with manageable adverse effects, based on the findings of an international phase 1/2 clinical trial spearheaded by researchers at Washington University School of Medicine in St. Louis.
The clinical trial investigated the safety and effectiveness of a cutting-edge CAR-T cell immunotherapy specifically formulated to target malignant T cells. Trial participants had been diagnosed with uncommon cancers—T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma—and had exhausted treatment options after standard therapies failed to yield results. With the new immunotherapy, a majority of the patients in the study who were administered the complete dose of cells achieved full remission of their cancer.
The trial’s findings were disclosed on May 30 in the journal Blood.
“For individuals with these rare and aggressive cancers, who lack other alternatives, this has the potential to represent a significant breakthrough in the field,” stated lead author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, who originally developed the therapy in his laboratory at the institution. “The trial revealed a substantial probability of response to the treatment and even remission. This CAR-T cell therapy is promising as a ‘bridge-to-transplant’ solution for patients who would otherwise not qualify for stem cell transplantation, the only potentially curative approach for these blood cancers.”
Further research involving larger patient cohorts and extended follow-up is essential before determining if this new therapy could offer a cure independently.
The current trial encompassed 28 adult and adolescent patients afflicted with T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma who either relapsed after undergoing multiple lines of treatment or never responded to any therapies. Approximately 1,000 individuals are diagnosed with these malignancies each year in the U.S. Should the cancer fail to respond to treatment or recur after initial therapy, patients typically survive only six months on average, with less than 7% reaching the five-year milestone.
The therapy, designated WU-CART-007, was created by Wugen, a biotech startup originating from WashU, founded by DiPersio and other WashU Medicine researchers, including Matthew Cooper, PhD, who co-established the firm when he was part of the WashU Medicine faculty and currently serves as Wugen’s chief scientific officer. Collaborating with WashU’s Office of Technology Management (OTM), they launched the company in 2018. The clinical trial was carried out in Australia, Europe, and various locations across the U.S. For the St. Louis site, the trial was hosted at the Siteman Cancer Center, affiliated with Barnes-Jewish Hospital and WashU Medicine.
The design of the trial included a dose-escalation phase, which established the recommended amount of therapeutic cells for the next phase of the study. Dose escalation is critical for determining the maximum amount of CAR-T cells that can be administered to patients without inducing severe side effects. Thirteen patients received the full dose of 900 million CAR-T cells following a procedure to deplete their own immune cells. This lymphodepletion process reduces immune cell levels, allowing room for the new therapeutic T cells to take root and multiply. During the study period, two of these patients succumbed to their cancer or complications arising from treatment, such as infections.
Among the 11 patients evaluated after treatment, the overall response rate was 91%, indicating that 10 patients exhibited no signs of cancer post-treatment or saw a substantial reduction in their cancer cell load. Eight out of 11 patients (72.7%) attained complete remission. At the study’s data cutoff, six who underwent a transplant remained in remission, showing no disease evidence six to 12 months later.
“These response and remission rates — ranging from 70%-90% of patients — are significantly higher than what is typically observed with standard treatment for this type of cancer, which generally results in remission for only 20%-40% of patients,” remarked first and corresponding author Armin Ghobadi, MD, a medicine professor and clinical director of the Center for Gene and Cellular Immunotherapy at WashU Medicine. “These results are exceptional, particularly since the trial participants had exhausted all other options. They faced very aggressive cancer recurrences after multiple treatment attempts, including several who relapsed following an earlier stem cell transplant.”
A majority of patients (88.5%) experienced cytokine release syndrome as an adverse effect of the immunotherapy, with these cases primarily classified as mild or moderate. Cytokine release syndrome is a frequent side effect of CAR-T cell therapy resulting from large groups of immune cells releasing chemicals that trigger a full-body inflammatory response. Approximately 19% of patients experienced more severe instances of cytokine release syndrome. A small number encountered rarer adverse effects, including neurotoxicity syndrome and low-grade graft-versus-host disease. Adverse events were addressed with supplementary therapies.
Off-the-shelf Cell Therapy
The immunotherapy assessed in this trial is referred to as a “universal” CAR-T cell therapy because it employs CRISPR gene-editing technology, allowing it to be produced from cells provided by any healthy donor and used for any patient diagnosed with a T cell cancer. Conversely, existing CAR-T cell therapies are derived from the patient’s own immune cells, necessitating the collection of cells from the patient and their transportation to a manufacturing facility, which then ships them back. This conventional process often takes three to six weeks. In contrast, universal CAR-T cell therapies can be pre-manufactured, cryogenically stored, and made readily available “off-the-shelf,” significantly cutting down the time before treatment can commence.
By utilizing CRISPR gene editing tools, the production process removes the T cell receptor from donor cells, thereby significantly lowering the risk of graft-versus-host disease, where donor T cells attack healthy tissue. Additionally, eliminating another key antigen hinders the CAR-T cells from attacking one another. The unique challenge posed by the rare cancers in this investigation lies in the fact that both the therapeutic cells and the cancer cells are T cells, necessitating precautionary measures to ensure the therapeutic T cells do not mistakenly identify one another as cancer cells, preventing CAR-T cell fratricide. All currently approved CAR-T cell therapies focus on B cell cancers, which do not encounter this T cell self-targeting issue. After employing CRISPR gene editing to alter the CAR-T cells and avert these detrimental side effects, the cells are further engineered to target a protein known as CD7 on the surface of malignant T cells, facilitating the destruction of the cancer.
“A larger international clinical trial for this therapy is already in progress,” DiPersio stated. “We must first complete this extensive trial, but we are optimistic that this universal CAR-T cell therapy may ultimately become an approved treatment for patients battling lethal T cell cancers.”
Ghobadi A, Aldoss I, Maude SL, Bhojwani D, Wayne AS, Bajel A, Dholaria B, Faramand R, Mattison RJ, Rijneveld A, Zwaan CM, Calkoen F, Baruchel A, Boissel N, Rettig M, Wood B, Jacobs K, Christ S, Irons H, Capoccia B, Masters D, Gonzalez J, Wu T, del Rosario M, Hamil A, Bakkacha O, Muth J, Ramsey B, McNulty E, Baughman J, Cooper ML, Davidson-Moncada J, DiPersio JF. Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory
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T cell neoplasms. Blood. May 30, 2025.
Ghobadi has offered consulting for Wugen. The founders of Wugen comprise members of Washington University physicians who are associates of Ghobadi. Numerous co-authors are personnel of Wugen, and several possess shares in the organization. DiPersio is a co-founder of Wugen and maintains equity-stake in the firm.
This study received financial backing from Wugen; along with support from the National Cancer Institute (NCI) of the National Institutes of Health (NIH), via an NCI Outstanding Investigator Award, grant number R35CA210084; an NCI Leukemia SPORE, grant number P50CA171963; and an NCI Research Specialist Award, grant number R50CA211466.
About Washington University School of Medicine
WashU Medicine is a worldwide leader in academic medicine, encompassing biomedical research, patient care, and educational initiatives with 2,900 faculty members. Its National Institutes of Health (NIH) research funding portfolio ranks second largest among U.S. medical colleges, having increased by 56% in the past seven years. Coupled with institutional funding, WashU Medicine dedicates over $1 billion each year to basic and clinical research advancements and education. Its faculty practice consistently ranks within the top five in the nation, featuring more than 1,900 faculty physicians practicing at 130 facilities and who also serve as the medical staff of Barnes-Jewish and St. Louis Children’s hospitals under BJC HealthCare. WashU Medicine boasts a rich history in MD/PhD education, recently allocated $100 million for scholarships and curriculum revitalization for its medical students, and hosts exemplary training programs across all medical subspecialties as well as physical therapy, occupational therapy, and audiology and communication sciences.
Originally published on the WashU Medicine website
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