Optimizing CAR-T cell manufacturing processes during pivotal clinical trials
Open accessAbstract
Tisagenlecleucel is a CD19-specific chimeric antigen receptor (CAR)-T cell therapy approved for patients aged ≤25 years with relapsed or refractory B cell precursor acute lymphoblastic leukemia (B-ALL) and adults with relapsed or refractory diffuse large B cell lymphoma (DLBCL). The initial tisagenlecleucel manufacturing process technology was developed at an academic center and was subsequently transferred, optimized, validated, and scaled out to supply large global trials before commercialization. Tisagenlecleucel manufactured in two centralized facilities has been successfully used in global multicenter trials for B-ALL and DLBCL (>50 clinical centers in 12 countries). In this paper, we describe some of the continuous process improvements made to tisagenlecleucel manufacturing over time to meet global demand while maintaining and improving product quality. During early tisagenlecleucel clinical trials, process enhancements were made to address logistical challenges related to manufacturing for multicenter trials and to accommodate the variability observed in patient starting cellular material. These enhancements resulted in improvements in manufacturing capacity, process robustness, manufacturing success rates, and product quality, and reductions in throughput time. In summary, through continuous evaluation and improvements based on experience during global trials, a consistent and robust commercial manufacturing process for tisagenlecleucel has been developed, leading to improvements in manufacturing success when compared to the initial processes.
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The turnaround vein-to-vein time for centralized CAR-T manufacturing is typically 3-5 weeks.
“The turnaround vein-to-vein time is typically 3−5 weeks,3”
From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [3]
The section “Manufacturing Success and Low Throughput Time with Optimized Tisagenlecleucel Commercial Manufacturing” (page unavailable) reports a median of 23 days and a range of 21–37 days for the first 37 commercial products, broadly consistent with 3–5 weeks. But it measures time from receipt of material at the manufacturing facility to return of product to the clinical site—not vein-to-vein time from collection to infusion—and concerns tisagenlecleucel rather than centralized CAR-T manufacturing generally. (LLM, conf=0.87)
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Noaks, E., Peticone, C., Kotsopoulou, E., & Bracewell, D. G. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.002 · Cited by 62 · see citing works
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- Authors
- Tyagarajan, S., Spencer, T., & Smith, J.
- Affiliations
- Novartis (United States) (US)
- Corresponding author
- Tyagarajan, Seshu
- Venue
- Molecular Therapy - Methods & Clinical Development
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 16
- Pages
- 136-144
- ISSN
- 2329-0501 (ISSN-L)
- PMC
- PMC6970133
- OpenAlex
- W2990473850
- Cited by
- 161
- References
- 2
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 26 · 2023: 24 · 2022: 23 · 2021: 31 · 2020: 7
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novartis Pharmaceuticals Corporation
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- tisagenlecleucel, CAR T cell manufacturing, CD19 CAR, B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, production process optimization, production capacity, process robustness, product quality
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