Using CRISPR to enhance T cell effector function for therapeutic applications.

Cytokine: X
Julian J Freen-van Heeren

Abstract

T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.

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Methods Mentioned

BETA
transgenic
genetic modification
xenograft
glycosylation

Related Concepts

Malignant Neoplasms
Clinical Trials
Interleukin-2
Neoplasms
T-Lymphocyte
Transcription, Genetic
Cytokine
Immunotherapy for Cancer
Cell Therapy
Tissue Engineering

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