World's First-in-Human Dosing of Off-the-Shelf CAR-NK Cells Enabled by Innovative mRNA-LNP Technology Offers New Hope for Cancer and Autoimmune Disease Treatment

Nov 27, 2023 07:20 CST Updated 07:20

ProMab Biotechnologies

Innovative Antibody Technology Developer

Recently, the "off-the-shelf" CAR-NK cells for the treatment of lymphoma, co-developed by ProMab Biotechnologies, Inc. and Hunan Jiyan Biotechnology Co., Ltd., have officially entered IIT clinical trials. Based on the powerful and stable transfection technology of mRNA-LNP, this project focuses on advancing the "off-the-shelf" CAR-NK therapy for B-cell lymphoma into the clinical stage. Currently, the first group of IIT patients has completed treatment, showing good safety.

Efficient NK Cell Expansion Technology

Through the improvement of culture methods, this project achieved low-generation and highly efficient NK cell expansion. FACS analysis showed that the proportion of CD56-positive and CD3-negative cells in the expanded NK cells exceeded 98%.

NK Cell Expansion Efficiency and Positivity Rate

NK Cell High-Efficiency Stable Transfection "Powerful Tool": mRNA-LNP Patent Technology

This project innovatively applies the mRNA-LNP patent technology to construct "off-the-shelf" CAR-NK cells, which hasWorld Leading AdvantageThe positive expression rate of CD19 in NK cells transfected with CD19-CAR based on mRNA-LNP technology can be significantly higher than that achieved using the original lentivirus transfection technology. By directly introducing mRNA into the cytoplasm, it achieves highly efficient gene transfection while avoiding the use of gene editing and viral vectors, thereby reducing potential safety risks. Meanwhile, by optimizing the design and therapeutic strategies of CAR-NK cells, their clinical efficacy can be further enhanced.

mRNA In Vitro Transcription and mRNA-LNP Transfection Efficiency

Preclinical in vitro data show that the "off-the-shelf" CD19-CAR-NK based on mRNA-LNP technology has a good killing effect on CD19-positive Daudi cells and leukemia cell lines; the in vivo xenograft tumor NSG mouse model shows that CD19-CAR-NK cells can effectively inhibit the growth of Nalm-6 xenograft tumors in the mouse model, laying a solid technical foundation for the initiation of IIT.

Preclinical Study Results

Currently, the project has successfully enrolled participants, with no observed CRS or inflammatory responses, and its clinical safety has been preliminarily validated. The next step will involve conducting IIT clinical trials using "off-the-shelf" CD19-CAR-NK cells based on mRNA-LNP technology to treat the autoimmune disease lupus erythematosus. Further development and optimization of treatment strategies and efficacy will be pursued by combining mRNA-LNP with CAR-NK technology. An "off-the-shelf" supply chain for CAR-NK cells will be established to further reduce production costs, enhance therapy accessibility, expand the range of indications, and benefit more patients. The tremendous application potential of mRNA-LNP delivery technology in the field of cell therapy is about to be revealed.

About ProMab Biotechnologies, Inc.

ProMab Biotechnologies has long-term expertise in antibody technology platforms, immunotherapy cell treatment platforms, and LNP delivery system platforms. It is one of the earliest expert teams globally to utilize LNP delivery systems for immunotherapy development. The company has developed a microfluidic platform for reproducible mRNA-LNP development, supporting all stages from mRNA sequence synthesis, screening, testing, and optimization to LNP formulation development and production. This platform has been successfully applied in fields such as mRNA vaccines, in vivo delivery of monoclonal/bispecific antibody drugs, and targeted therapy development like CAR-T/NK. A series of off-the-shelf mRNA-LNP products have been developed for customers' research and experimental use. Additionally, the company offers customized services for specific genes of interest to clients. To date, ProMab has served global clients in the mRNA-LNP field, including UC San Diego, City of Hope, StemCell, JnJ, Stanford, and Novartis.

About Hunan Jiyan Biotechnology Co., Ltd.

Hunan Jiyan Biotechnology Co., Ltd. is one of the few companies in China and even globally that has pioneered the application of mRNA-LNP delivery technology to develop off-the-shelf universal CAR-NK cell therapies. Equipped with two "powerful tools"—off-the-shelf universal CAR-NK cells and high-payload effective delivery technology—the company is strategically targeting autoimmune diseases, cancer, and aging-related conditions. To date, the company has received approval for two ethical clearances to conduct investigator-initiated clinical trials (IIT) and has completed initial clinical observations on the first group of patients, verifying the drug's safety. As research into the therapeutic efficacy of off-the-shelf universal CAR-NK cell therapies progresses, it holds the potential to fundamentally address the current challenges faced by CAR-T cell therapies, such as long production times and high costs, ultimately making immunocyte treatments accessible to the general public.