Assessing a single-cell multi-omic analytic platform to characterize ex vivo-engineered T-cell therapy products

Area of Science:

• Cellular and Molecular Biology
• Genomics and Bioinformatics
• Immunotherapy and Cancer Research

Background:

• Genetically engineered CD8+ T cells show promise for cancer treatment.
• Assessing product safety and heterogeneity is challenging for these therapies.
• Current bulk sequencing methods cannot detect rare off-target genetic events.

Purpose of the Study:

• To develop a single-cell multi-omics assay for comprehensive characterization of genetically engineered cell products.
• To enable precise assessment of on-target edits, off-target events, and translocations.
• To enhance safety and genotoxicity evaluations for cell-based therapies.

Main Methods:

• Development of a single-cell multi-omics assay integrating DNA and protein analysis.
• Application of the assay to characterize genetically engineered cell products.
• Quantification of genetic modifications at the single-cell level.

Main Results:

• The assay successfully quantified on-target edits with single-cell resolution.
• Off-target events and potential translocations were identified at the per-cell level.
• Detailed characterization data for the final cell product was generated.

Conclusions:

• A single-cell multi-omics approach offers the necessary resolution for cellular product analysis.
• This method is vital for understanding product composition and identifying critical quality attributes (CQAs).
• The assay advances the safety assessment of genetically engineered cell therapies.