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Automated manufacture of ΔNPM1 TCR-engineered T cells for AML therapy.
Yonezawa Ogusuku, Isabella Elias; Herbel, Vera; Lennartz, Simon; Brandes, Caroline; Argiro, Eva; Fabian, Caroline; Hauck, Carola; Hoogstraten, Conny; Veld, Sabrina; Hageman, Lois; Teppert, Karin; Koutsoumpli, Georgia; Griffioen, Marieke; Mockel-Tenbrinck, Nadine; Schaser, Thomas; de Groot, Rosa; Johnston, Ian C D; Lock, Dominik.
Afiliación
  • Yonezawa Ogusuku IE; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Herbel V; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Lennartz S; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Brandes C; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Argiro E; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Fabian C; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Hauck C; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Hoogstraten C; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Veld S; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Hageman L; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Teppert K; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Koutsoumpli G; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Griffioen M; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Mockel-Tenbrinck N; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Schaser T; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • de Groot R; Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Johnston ICD; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
  • Lock D; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
Mol Ther Methods Clin Dev ; 32(2): 101224, 2024 Jun 13.
Article en En | MEDLINE | ID: mdl-38516690
ABSTRACT
Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure. Therefore, this study specifically addressed the requirements for a scaled manufacture of ΔNPM1-specific T cells in an automated, closed, and good manufacturing practice-compliant process. Starting from cryopreserved leukapheresis, 2E8 CD8-positive T cells were enriched, activated, lentivirally transduced, expanded, and finally formulated. By adjusting and optimizing culture conditions, we additionally reduced the manufacturing time from 12 to 8 days while still achieving a clinically relevant yield of up to 5.5E9 ΔNPM1 TCR-engineered T cells. The cellular product mainly consisted of highly viable CD8-positive T cells with an early memory phenotype. ΔNPM1 TCR CD8 T cells manufactured with the optimized process showed specific killing of AML in vitro and in vivo. The process has been implemented in an upcoming phase 1/2 clinical trial for the treatment of NPM1-mutated AML.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Methods Clin Dev Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Methods Clin Dev Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos