Cancer treatment has advanced with the introduction of a novel therapy using off-the-shelf anti-CD19 CAR-engineered double-negative T cells (RJMty19) to target relapsed or refractory large B-cell lymphoma. This innovative approach aims to overcome the limitations of traditional autologous CAR-T cell therapies, which are often expensive, time-consuming, and inaccessible to many patients.

A research team led by Dr. Wenbin Qian from department of hematology, the second affiliated hospital, school of medicine, Zhejiang University and Dr. Liming Yang from Wyze Biotech Co. Ltd, and their colleagues have conducted a first-in-human, phase 1 clinical trial to assess the safety and efficacy of this innovative treatment. Their work is published in the peer-reviewed journal eClinicalMedicine.

The study enrolled a small group of patients with relapsed or refractory large B-cell lymphoma who had undergone multiple previous lines of therapy. These patients received a single dose of RJMty19 after undergoing lymphodepleting chemotherapy. The researchers evaluated different dose levels to determine the optimal dosage. Remarkably, the trial found no dose-limiting toxicities, indicating a favorable safety profile.

In terms of efficacy, the highest dose level demonstrated impressive results. Dr. Yang highlighted the significance of these findings: “Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted.”

Notably, the study reported an overall positive response, with significant benefits seen at higher doses. Patients who received the highest doses showed the most significant benefits, with all patients at these levels achieving disease control and objective responses. This dose-dependent efficacy is a crucial finding that underscores the potential of RJMty19 as a viable treatment option for patients with large B-cell lymphoma.

The researchers observed that the treatment’s most common adverse effects were hematologic toxicities, including reductions in certain blood cell counts, which are manageable and expected with such therapies. Importantly, there were no severe cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), which are often concerns with CAR-T therapies.

Dr. Yang emphasized the potential impact of their work: “This phase 1 trial is a critical step towards providing an accessible and effective treatment for patients with relapsed or refractory large B-cell lymphoma. The promising results warrant further investigation in larger clinical trials.”

The study’s findings suggest that RJMty19 could revolutionize the treatment landscape for large B-cell lymphoma by providing a more accessible and potentially more effective option than current therapies. As researchers move forward with larger trials, the oncology community eagerly awaits further validation of these promising results.

In conclusion, this research by Dr. Qian and Dr. Yang, and the other experts offers hope to patients with relapsed or refractory large B-cell lymphoma, highlighting the potential of CD19-CAR-DNT cells as a new frontier in cancer immunotherapy. The study paves the way for future advancements and underscores the importance of innovative approaches in the fight against cancer.

Journal Reference

Xibin Xiao, Hui Liu, Xi Qiu, Panpan Chen, Xian Li, Dan Wang, Guangrong Song, Yu Cheng, Liming Yang, and Wenbin Qian. “CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study.” eClinicalMedicine, 2024. DOI:

About The Authors

Dr. Liming Yang is the Co-founder and Chairman at Wyze Biotech Co., Ltd, a China based clinic stage company, engaged in the development and commercialization of a novel off-the-shelf allogeneic DNT (Double Negative T) cells immunotherapies to improve the lives of cancer/autoimmune diseases patients and their overall survival by leveraging the clinically validated DNT cell technology. There are now five first-in-class and first-in-human phase I/II clinic trials to treat hematological malignancies and autoimmune diseases in China and had shown its promising safety and efficacy profile. The results from the allogeneic DNT cells immunotherapy so far have practice-changing implications for the field of oncology by improving survival rates and drastically expanding patient access to treatment. Several novel CAR-DNT cell products based on the off-the-shelf characteristics of DNT cells are in the late-stage preclinical stages.

Dr. Yang was associate director of product development in Stemgent and quality control manager in BD Biosciences Pharmingen, both based in San Diego, California, USA. He also worked previously as postdoctoral fellow at University of Toronto, Canada on DNT cell project and is one of the key inventors of DNT technology. Dr. Yang served as PI and associate professor when he worked in Medical School of Shanghai Jiaotong University in China in mid 1990s. He received his M.D. from the Medical School at the Zhejiang University in China and finished his joint Ph.D. program of Shanghai Jiaotong University and University of Toronto in Immunology. Dr. Yang has published more than 30 papers in peer-reviewed journals including co-first author in Nature Medicine and is an inventor on more than 10 patent applications in the field of DNT Technology.

Wenbin Qian, PhD., MD., Director, Department of Hematology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Chairman, Hematology Branch of the Zhejiang province Medical Association. His specific expertise is in the cell therapies with a focus on CAR-T and CAR-NK cells. He has authored over 90 peer review papers in leading international journals.