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Cited by 88CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients

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Maschan, Michael, Caimi, Paolo F., Reese-Koc, Jane, Sanchez, Gabriela Pacheco, Sharma, Ashish A., Molostova, Olga, Shelikhova, Larisa, Pershin, Dmitriy +19 more·2021·Nature Communications
DOI 10.1038/s41467-021-27312-6PMC PMC8664838
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Abstract

Chimeric antigen receptor (CAR) T cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of the 4-1BB co-stimulatory and TNFRSF19 transmembrane domains, showing anti-tumor efficacy in an in vivo xenograft lymphoma model. CAR19 T cells are manufactured under current good manufacturing practices (cGMP) at two disparate clinical sites, Moscow (Russia) and Cleveland (USA). The CAR19 T-cells is used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL; n = 31) or adult B-cell Lymphoma (NHL; n = 23) in two independently conducted phase I clinical trials with safety as the primary outcome (NCT03467256 and NCT03434769, respectively). Probability of measurable residual disease-negative remission was also a primary outcome in the ALL study. Secondary outcomes include complete remission (CR) rates, overall survival and median duration of response. CR rates are 89% (ALL) and 73% (NHL). After a median follow-up of 17 months, one-year survival rate of ALL complete responders is 79.2% (95%CI 64.5‒97.2%) and median duration of response is 10.2 months. For NHL complete responders one-year survival is 92.9%, and median duration of response has not been reached. Place-of-care manufacturing produces consistent CAR-T cell products at multiple sites that are effective for the treatment of patients with B-cell malignancies.

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  • The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines.

    “The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines and was previously used in numerous clinical studies.26,27,28”

    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 [27]

    The Methods section (page unavailable) says lentiviral vectors were manufactured. The Discussion (page unavailable) describes the CAR-T cell manufacturing system as GMP-compliant, but does not say the lentiviral vector itself was manufactured and tested under a GMP-compliant quality management system. (LLM, conf=0.84)

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Cited by

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Authors
Maschan, M., Caimi, P. F., Reese-Koc, J., Sanchez, G. P., Sharma, A. A., Molostova, O., Shelikhova, L., Pershin, D., Stepanov, A., Muzalevskii, Y., Suzart, V. G., Otegbeye, F., Wald, D., Xiong, Y., Wu, D., Knight, A., Oparaocha, I., Ferencz, B., Roy, A., Worden, A., Kruger, W., Kadan, M., Schneider, D., Orentas, R., Sekaly, R.-P., de Lima, M., & Dropulić, B.
Affiliations
  • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU)
  • Cleveland Clinic (US)
  • Emory University (US)
  • Institute of Bioorganic Chemistry (RU)
  • University Hospitals Seidman Cancer Center (US)
  • Lentigen Technology (United States) (US)
  • Seattle Children's Hospital (US)
Corresponding author
Dropulić, Boro
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-12-10
Volume
12
Issue
1
Pages
7200-7200
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-27312-6
PMC
PMC8664838
OpenAlex
W4200414258
Cited by
88
References
6
Citations by year
2026: 24 · 2025: 14 · 2024: 25 · 2023: 15 · 2022: 10
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
CD19 CAR T cells, B-cell acute lymphoblastic leukemia, non-Hodgkin lymphoma, minimal residual disease, complete remission, relapsed/refractory B-cell malignancies, CAR T cell safety, current good manufacturing practice
MeSH terms
Receptors, Chimeric Antigen, Progression-Free Survival, Adolescent, Adult, Aged, Animals, B-Lymphocytes, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Receptors, Antigen, T-Cell, Russia, T-Lymphocytes, United States, Lymphoma, B-Cell, Mice, Inbred NOD, Receptors, Tumor Necrosis Factor, Neoplasm, Residual, Antigens, CD19, Mice, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Young Adult

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