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Review
. 2017 Jun 24;5:22.
doi: 10.1186/s40364-017-0102-y. eCollection 2017.

Engineering CAR-T Cells

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Free PMC article
Review

Engineering CAR-T Cells

Cheng Zhang et al. Biomark Res. .
Free PMC article

Abstract

Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated in other hematologic malignancies and solid tumors. CAR-T cells are generated by the T cells from patients' or donors' blood. After the T cells are expanded and genetically modified, they are reinfused into the patients. However, many challenges still need to be resolved in order for this technology to gain widespread adoption. In this review, we first discuss the structure and evolution of chimeric antigen receptors. We then report on the tools used for production of CAR-T cells. Finally, we address the challenges posed by CAR-T cells.

Keywords: CAR-T cells; Chimeric antigen receptor redirected T cells; Evolution; Production; Structure; Viral vector.

Figures

Fig. 1
Fig. 1
Structure of chimeric antigen receptor (CAR). The CAR includes ectodomain, transmembrane domain and endodomain
Fig. 2
Fig. 2
Evolution of chimeric antigen receptor (CAR) from the first generation to the fourth generation. Single chain antibody (CD3ζ or FcεRIγ) links the ITAM at transmembrane region for the first generation. Costimulatory molecule (CM1), such as CD28, has been engineered to the signal transduction region for the second generation. Another costimulatory molecule (CM2) based on the second generation for the third generation has been engineered to the signal transduction region, such as combining CD134 or CD137. The interleukin-12 (IL-12) based on the second generation for the fourth generation has been engineered to the signal transduction region. ITAM: Immunoreceptor tyrosine-based activation motifs

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