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Assessing a single-cell multi-omic analytic platform to characterize ex vivo-engineered T-cell therapy products.
Moshref, Maryam; Lo, Jerry Hung-Hao; McKay, Andrew; Camperi, Julien; Schroer, Joseph; Ueno, Norikiyo; Wang, Shu; Gulati, Saurabh; Tarighat, Somayeh; Durinck, Steffen; Lee, Ho Young; Chen, Dayue.
Afiliación
  • Moshref M; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
  • Lo JH; Oncology Bioinformatics, Genentech, South San Francisco, CA, United States.
  • McKay A; Pharma Technical Development Bioinformatics, Genentech, South San Francisco, CA, United States.
  • Camperi J; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
  • Schroer J; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
  • Ueno N; Cell and Gene Therapy Business Unit, Mission Bio, South San Francisco, CA, United States.
  • Wang S; Bioinformatics Department, Mission Bio, South San Francisco, CA, United States.
  • Gulati S; Bioinformatics Department, Mission Bio, South San Francisco, CA, United States.
  • Tarighat S; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
  • Durinck S; Oncology Bioinformatics, Genentech, South San Francisco, CA, United States.
  • Lee HY; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
  • Chen D; Cell Therapy Engineering and Development, Genentech, South San Francisco, CA, United States.
Front Bioeng Biotechnol ; 12: 1417070, 2024.
Article en En | MEDLINE | ID: mdl-39229457
ABSTRACT
Genetically engineered CD8+ T cells are being explored for the treatment of various cancers. Analytical characterization represents a major challenge in the development of genetically engineered cell therapies, especially assessing the potential off-target editing and product heterogeneity. As conventional sequencing techniques only provide information at the bulk level, they are unable to detect off-target CRISPR translocation or editing events occurring in minor cell subpopulations. In this study, we report the analytical development of a single-cell multi-omics DNA and protein assay to characterize genetically engineered cell products for safety and genotoxicity assessment. We were able to quantify on-target edits, off-target events, and potential translocations at the targeting loci with per-cell granularity, providing important characterization data of the final cell product.

Conclusion:

A single-cell multi-omics approach provides the resolution required to understand the composition of cellular products and identify critical quality attributes (CQAs).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Bioeng Biotechnol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
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: Front Bioeng Biotechnol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza