June 25, 2025

Addressing the Bottlenecks in T-Cell Activation—A GMP-Ready Solution for Cell Therapy Developers

In the development of CAR-T and TCR-T therapies, few steps are as critical—and as vulnerable—as T cell activation. Clinical-stage cell therapy teams frequently encounter challenges with inconsistent activation efficiency, batch variability, and reagent quality. These issues not only delay timelines but also increase regulatory and financial risk.

One such case emerged during the early-stage development of a new CAR-T therapy targeting solid tumors. Despite meticulous upstream processing and the use of well-established activation reagents, the team encountered activation rates below 50% and highly variable expansion results—forcing them to repeat key production runs and postpone their IND submission.

This scenario is far from unique.

The Challenge: Reagent Variability and Incomplete Activation

Commercially available CD3/CD28 beads, while widely used, often fall short in clinical manufacturing environments. Issues include:

- Incomplete activation leading to suboptimal CD25/CD69 expression

- Batch inconsistency impacting reproducibility

- Additional preparation steps (e.g., pre-washing, reconstitution) increasing time and risk

- Limited regulatory documentation for global submission support

These inefficiencies compound over time—delaying timelines, complicating quality control, and increasing cost per dose.

The Solution: ActSep® CD3/CD28 Magnetic Beads and ActCel™ Activator

T&L Biotechnology’s ActSep® CD3/CD28 Magnetic Beads and ActCel™ T Cell Activator were developed to address these challenges directly in GMP and translational environments.

ActSep® CD3/CD28 Beads offer:

- GMP-grade, FDA-DMF registered product (DMF No. 038124)

- 4.5 μm ultra-superparamagnetic particles combining T cell isolation and activation in one step

- Single-vial format with flexible volumes, eliminating the need for custom aliquoting

- Performance-proven results: >85% activation efficiency and >300x expansion in 14-day protocols

Complementing this, ActCel™ is a ready-to-use nanomatrix functionalized with anti-CD3 and anti-CD28 antibodies:

- Stable, no pre-washing required

- Compatible with both fresh and cryopreserved PBMC

- High activation and expansion outcomes equivalent to—or exceeding—top global competitors

Clinical Validation: From Research to IND Approval

The performance of the ActSep® system is not theoretical. In 2024, Yimiao Bio’s IM96 CAR-T cell injection—a novel therapy for metastatic colorectal cancer—was submitted for IND approval using T&L’s CD3/CD28 beads as a critical reagent. The application was accepted by the National Medical Products Administration (NMPA), marking the first time a domestic microbead product was used in a CAR-T IND submission in China.

To date, the ActSep® platform has supported:

- 50+ clinical and translational users

- 5 successful GMP audits

- 30+ projects requiring regulatory documentation

Summary

For cell therapy manufacturers, reagent selection is no longer a back-office decision. It is central to product consistency, regulatory success, and commercial scalability.

T&L’s T cell activation portfolio—centered on ActSep® and ActCel™—offers a GMP-compliant, high-performance alternative to traditional platforms, ensuring your clinical programs move forward with confidence.