Francisco Conesa Buendía: CAR-T Cell Manufacturing – From Low-Seed to High-Yield in 7 Days
Francisco Conesa Buendía, Assistant in Cell and Gene Therapies Manufacturing at Memorial Sloan Kettering Cancer Center, shared an article by Kurt Marshall, et al. on LinkedIn:
“CAR-T Cell Manufacturing: From Low-Seed to High-Yield in 7 Days.
The demand for CAR-T cell therapy is soaring, but manufacturing bottlenecks continue to limit patient access. Traditional production methods struggle with long turnaround times, high costs, and variability in patient starting material.
A recent study using the Quantum Flex Cell Expansion System (Terumo Blood and Cell Technologies) demonstrated a GMP-compliant hollow-fiber bioreactor platform capable of achieving high-yield, low-seed CAR-T expansion in 7 days.
Key Findings & Data:
Expansion from Low-Seed Starting Material
- As little as 1 million T cells expanded to a maximum of 2.6 billion CAR-T cells (150-200x fold increase).
- Consistent expansion across multiple runs (1M, 3M, 6M, 15M cells).
- Ability to support adult, pediatric, and compassionate-use dosing requirements.
High Viability, Strong Potency
- 93% cell viability across all expansions.
- Post-thaw viability: 86.8% (for example, above the 80% FDA requirement for Kymriah).
- Robust Granzyme B & IFN-γ secretion, ensuring potent tumor-killing capability.
Efficient, Closed-System Automation
- Hollow-fiber bioreactor allows for optimized nutrient exchange & gas control.
- Only 1.7 L of complete medium required per expansion, reducing culture medium and cytokine costs.
Clinically Relevant Cytotoxicity
- CAR-T cells eliminated ~90% of CD19+ tumor cells at a 2.5:1 effector-to-target ratio.
- Maintained early memory T cell phenotypes critical for long-term efficacy.
Why This Matters for CAR-T Manufacturing:
Low-Seed Expansion = More Patients Eligible
Apheresis failures due to low T cell counts can disqualify patients from CAR-T therapy. This study proves that as little as 1% of an expected apheresis yield can be expanded to clinically viable doses, helping more patients receive treatment.
Decentralized vs. Centralized Manufacturing?
Centralized production is costly and logistically complex. Decentralized models using functionally closed, automated systems could reduce lead times and increase accessibility.
Beyond Oncology: The Next Frontier
CAR-T is moving beyond hematologic cancers into solid tumors and even autoimmune diseases (SLE, myasthenia gravis). Flexible, GMP-ready bioreactor platforms could be critical for this expansion.
What’s Next?
- Can automated expansion platforms help reduce the cost of CAR-T therapy?
- Will decentralized manufacturing be the future standard for cell therapy production?
- How can we further reduce time-to-dose and improve patient access?”
Rapid manufacture of low-seed CAR-T cells in a GMP-grade hollow-fiber bioreactor platform.
Authors: Kurt Marshall, et al.
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