Data Entry Maintenance

Metadata Commons Identifier

HMC000110

Project Title

RNA-seq comparison of YT-Indy based reconstituted cytotoxic T cells and primary activated CD8+ T cells

Project Description

<p>Current tools for functionally profiling T cell receptors with respect to cytotoxic potency and cross-reactivity are hampered by difficulties in establishing model systems to test these proteins in the contexts of different HLA alleles and against broad arrays of potential antigens. We have implemented a granzyme-activatable sensor of T cell cytotoxicity in a universal prototyping platform which enables facile recombinant expression of any combination of TCR-, peptide-, and class I MHC-coding sequences and direct assessment of resultant responses. This system consists of an engineered cell platform based on the immortalized natural killer cell line, YT-Indy, and the MHC-null antigen-presenting cell line, K562. These cells were engineered to furnish the YT-Indy/K562 pair with appropriate protein domains required for recombinant TCR expression and function in a non-T cell chassis, integrate a fluorescence-based target-centric early detection reporter of cytotoxic function, and deploy a set of protective genetic interventions designed to preserve antigen-presenting cells for subsequent capture and downstream characterization. As part of the development of the system, we conducted an RNA-seq study to characterize transcript expression in the base YT-Indy cell line, the genome engineered YT-rCTL version in the presence or absence of cognate antigen-presenting cells, and primary tissue derived TCR-T comparator cells in the presence or absence of cognate antigen-presenting cells. These data represent a supplement to the bioRxiv pre-print (<a href="https://www.biorxiv.org/content/10.1101/2023.11.20.567960v1">DOI 10.1101/2023.11.20.567960</a>) and the final published version in <a href="https://www.nature.com/articles/s41698-024-00669-9">npj Precision Oncology (2024)</a>. An identical dataset corresponding to this entry has also been previously deposited in the <a href="https://zenodo.org/records/8428844">Zenodo repository (DOI 10.5281/zenodo.8428843</a>).<br><br>Genome BC project code: PIF005</p>

Project Funder(s)

Genome British Columbia, Michael Smith Health Research BC, NIH

Project Institution(s)

BC Cancer Research Institute

Project Investigator(s)

Robert Holt, Govinda Sharma

Data Access Request URL*

Keywords

adaptive immunity, T cell receptor, natural killer cells, TCR-T cells, leukemic cell line

Publication Link

https://pubmed.ncbi.nlm.nih.gov/39160299

Study Completed

Post to REACH BC Platform

Cohort Name

YT-Indy based reconstituted cytotoxic T cells and primary activated CD8+ T cells

Cohort Size

Disease/Condition Studied

acute lymphoblastic leukemia

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Clinical Data Types Available

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