Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Harnessing the Transcriptional Signatures of Car-T Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies

Version 1 : Received: 23 December 2023 / Approved: 5 January 2024 / Online: 5 January 2024 (10:37:47 CET)

A peer-reviewed article of this Preprint also exists.

Liao, Y.-M.; Hsu, S.-H.; Chiou, S.-S. Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies. Int. J. Mol. Sci. 2024, 25, 2416. Liao, Y.-M.; Hsu, S.-H.; Chiou, S.-S. Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies. Int. J. Mol. Sci. 2024, 25, 2416.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We will examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Keywords

Single-cell sequencing technologies; CAR-T therapy; Tumor microenvironment; Transcriptional complexity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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