Opening a new horizon in cancer immunotherapy of high stability and effectiveness with new T cell modification system

A team, led by Professor Chung Aram, develops a T cell modification system.

The team introduces a microfluidic cell hydroporator platform that can manufacture cancer immune-cell therapies.

Research results are published in the Nano Letters.

▲ (From left) Professor Chung Aram (Korea University, MxT Biotech, co-corresponding author), Hur Jeongsoo (Korea University, first author), Kim Hyelee (Korea University, co-second author), Kim Ui-jin (University of Seoul, co-second author), Professor Lee Dong-sung (University of Seoul , co-corresponding author)

The team, led by Professor Chung Aram from the Department of Bioengineering at Korea University, has developed a T-cell gene modification system for cancer immunotherapy. The platform is notable for its exceptional cellular stability and throughput. Their research results were published online in Nano Letters, an international scientific journal with an Impact Factor of 10.8, on July 28.

  
Amid the challenges associated with achieving a complete response to cancer using conventional toxic chemotherapy and targeted treatments, cancer immuno-cell therapy has emerged as a prominent approach. This method utilizes the patient's own immune cells to eliminate cancer, and shows remarkable efficacy, particularly in the case of hematologic malignancies. As a result, thus far six immune cell therapies have been approved by the U.S. FDA, and they are currently being applied in medical institutions in South Korea for the treatment of hematologic cancer patients.

In typical cancer immunotherapy, a patient's T-cells are isolated, and chimeric antigen receptor (CAR) genes are introduced to create CAR-T cells capable of precisely identifying and targeting cancer cells. These modified T-cells are then reintroduced into the patient's body. To deliver the genes into the cells, viruses or electroporation methods are commonly used. However, these conventional approaches have drawbacks, particularly cost, gene delivery efficiency, and cell stability after delivery.

To address these limitations, Professor Chung Aram's team developed a hydroporator platform for manufacturing immunotherapy using T-cells. The system utilizes a specific fluid flow within microfluidic channels to open both cell and nuclear membranes, allowing the transfer of genes into cells.

This technology boasts impressive efficiency in delivering different types of substances, processing over a million units per minute. Additionally, it leads to greater post-delivery T-cell stability than traditional electroporation methods, indicating its potential as an advanced immunotherapy production platform. Currently, Professor Chung Aram is actively engaged in commercializing the Hydroporator through MxT Biotech, a startup that originated from a laboratory in March 2021.

▲ Figure Description: Hydroporator operation principle, delivery results, and post-processing cellular stability analysis compared to electroporation

Kim Hyelee, the second author of the paper, stated, “Existing platforms for manufacturing immunotherapies, such as viruses and electroporation, fall short in achieving both high cellular stability and economic efficiency.” She further noted, “The potential demonstrated by the platform to overcome the limitations of previous methods could open up new horizons for the treatment of hematologic cancers and solid tumors.”

This research was conducted as joint research involving both Professor Lee Dong-sung from the Department of Life Sciences at University of Seoul, and Professor Cho Duck from the Department of Laboratory Medicine and Genetics, with grants from the Samsung Research Funding and Incubation Center for Future Technology, the National Research Foundation of Korea (Mid-Career), the Technological Innovation R&D Program, and the Materials/Parts Technology Development Program.
* Paper Title: Genetically Stable and Scalable Nanoengineering of Human Primary T Cells via Cell Mechanoporation
* Paper Link : https://pubs.acs.org/doi/10.1021/acs.nanolett.3c01720
* Authors: Hur Jeongsoo (Korea University, first author), Kim Hyelee (Korea University), Kim Uijin (University of Seoul), Kim Gi-beom (Korea University, MxT Biotech), Kim Jinho (Samsung Medical Center), Joo Byeongju (MXTE BioTech), Cho Duck (Samsung Medical Center), Lee Dong-sung (University of Seoul, co-corresponding author), Chung Aram (Korea University, MxT Biotech, co-corresponding author).