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

Michael Maschan, Paolo F. Caimi, Jane Reese-Koc, Gabriela Pacheco Sanchez, Ashish A. Sharma, Olga Molostova, Larisa Shelikhova, Dmitriy Pershin, Alexey Stepanov, Yakov Muzalevskii, Vinicius G. Suzart, Folashade Otegbeye, David Wald, Ying Xiong, Darong Wu, Adam Knight, Ibe Oparaocha, Beatrix Ferencz, Andre Roy, Andrew Worden, Winfried Kruger, Michael Kadan, Dina Schneider, Rimas Orentas, Rafick-Pierre Sekaly, Marcos Lima () and Boro Dropulić ()
Additional contact information
Michael Maschan: Oncology and Immunology
Paolo F. Caimi: Case Western Reserve University
Jane Reese-Koc: Case Western Reserve University
Gabriela Pacheco Sanchez: Emory University
Ashish A. Sharma: Emory University
Olga Molostova: Oncology and Immunology
Larisa Shelikhova: Oncology and Immunology
Dmitriy Pershin: Oncology and Immunology
Alexey Stepanov: Oncology and Immunology
Yakov Muzalevskii: Oncology and Immunology
Vinicius G. Suzart: Case Western Reserve University
Folashade Otegbeye: Case Western Reserve University
David Wald: Case Western Reserve University
Ying Xiong: Lentigen, A Miltenyi Biotec Company
Darong Wu: Lentigen, A Miltenyi Biotec Company
Adam Knight: Lentigen, A Miltenyi Biotec Company
Ibe Oparaocha: Lentigen, A Miltenyi Biotec Company
Beatrix Ferencz: Lentigen, A Miltenyi Biotec Company
Andre Roy: Lentigen, A Miltenyi Biotec Company
Andrew Worden: Lentigen, A Miltenyi Biotec Company
Winfried Kruger: Lentigen, A Miltenyi Biotec Company
Michael Kadan: Lentigen, A Miltenyi Biotec Company
Dina Schneider: Lentigen, A Miltenyi Biotec Company
Rimas Orentas: Lentigen, A Miltenyi Biotec Company
Rafick-Pierre Sekaly: Emory University
Marcos Lima: Case Western Reserve University
Boro Dropulić: Lentigen, A Miltenyi Biotec Company

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27312-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27312-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27312-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().