Q&A Session After Class | Unlocking The Code For Cost Reduction And Efficiency Enhancement Of CAR-T To Improve Accessibility Of Cell Therapy

On November 7th, we held the 2nd Session of Panda Class – CGT Series Lectures. For this session, we specially invited Dr. Xu Lei from Obio Technology to deliver a presentation themed Challenges and Solutions for Improving the Accessibility of CAR-T Therapy. During the lecture, Dr. Xu Lei elaborated on the clinical application outcomes of CAR-T therapy, discussed the challenges it faces such as production costs, manufacturing time and cell quality, and explored the future development trends of autologous CAR-T therapy; meanwhile, he proposed multiple optimization strategies for CAR-T manufacturing processes. In addition, during this live lecture, Manager Chen Xiaodong gave a detailed introduction to BioEngine's new immune cell culture medium product-HIPP-X100, including its characteristics and performance advantages in immune cell expansion. HIPP-X100 has achieved significant improvements in immune cell expansion rate, positive rate, memory phenotype and exhaustion phenotype.

Participants actively engaged in interactions during the live session, and Dr. Xu Lei provided detailed answers to many questions. Unfortunately, due to time constraints, not all questions could be addressed. We hereby compile and summarize the questions raised in the live broadcast.

Questions Related to CAR-T Manufacturing Processes

Q: What is the changing trend of CAR+ cells during the manufacturing process?

A: The performance may vary across different projects. In some cases, the expression of CAR+ cells gradually increases over time and then stabilizes. In other cases, the expression of CAR+ cells rises gradually, plateaus, and then decreases slightly in the later stage. This may be correlated with the viral vector and the activation and culture system.

Q: How fast should the CAR-T expansion rate be to significantly shorten the expansion time?

A: This needs to be viewed dialectically. For traditional CAR-T therapy, since cells need to reach a certain expansion scale before harvesting, a faster cell expansion rate enables earlier harvesting, reducing the occupation of workshop facilities and personnel. For rapid manufacturing processes, the shorter process duration is not caused by accelerated expansion. Instead, the products manufactured via rapid processes have robust expansion capability after being infused into the human body, allowing for a substantial reduction in the administration dose. Therefore, there is no need to prepare a large number of cells in vitro, thus omitting the in vitro expansion step.

Q: Besides expansion time, what other aspects should be considered when evaluating a CAR-T manufacturing platform?

A: Ultimately, the drug is intended for patient infusion, so safety and efficacy must be guaranteed. On this premise, the urgent industry challenge to address is the extremely high manufacturing cost per batch, which limits product accessibility. Therefore, minimizing manufacturing costs under the prerequisite of compliant production has become a common goal pursued by the industry.

Questions Related to Cytotoxicity Assays

Q: What equipment is used to detect the cell killing rate? Is RTCA adopted?

A: It mainly depends on the type of target cells and the principle of the method. For adherent target cells in general, the RTCA-based cytotoxicity culture system can be selected. For suspension target cells, since they are non-adherent, methods such as CAM staining and LDH assay can be adopted, followed by detection using flow cytometers and microplate readers.

Q: What types of cells are generally used in cytotoxicity assays?

A: Target cells with positive expression of specific antigens are used. These can be naturally isolated cells or in vitro constructed target cells with positive antigen expression.