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miRNAs play an important role in T-cell proliferation and differentiation. For example, some research utilizes miRNAs silencing inhibitory receptor transcripts to overcome T cell-intrinsic dysregulations and promote tumor regression. Therefore, the introduction of miRNA cassette in a CAR vector can overcome barriers limiting CAR T cell effectiveness and enhance the effector function of CAR-T cells. At Creative Biolabs, we are committed to developing ground-breaking cell therapies. Based on the CAR-T platform, we have developed a miRCAR-T platform involving the overexpression of miRNA within CAR-T cells. The miRCAR platform may offer a simpler, more effective, and more efficient method for cancer therapies.
A miRCAR construct involves the coexpression of miRNA genes with a CAR gene in T cells. The construction of a miRCAR can be achieved through a variety of strategies shown in Fig.1. A miRCAR construct can use a single DNA cassette or two separate viral vectors to encode the selected miRNA and CAR. The all-in-one vector is usually better than separate vectors.
The elements required in a miRCAR
Fig.1 Strategies of all-in-one miRCAR vector design.1
The miRNAs can regulate T cell functions by several mechanisms. The overexpression of specific miRNAs in CAR T cells can:
The following are some important miRNAs that can potentially modulate the function of T cells. These miRNA candidates combined with a CAR have the potential to improve the antitumor immune responses.
| miRNAs: | miR-214 | miR-146a | miR-23a | miR-150 | miR-155 |
| Target: | PTEN | NF-κB | Blimp-1 | IL-2Rα, ARRB2 | SHIP-1, SOCS-1 |
| miRNAs: | miR-143 | miR-17-92 | miR-15/16 | miR-342 | miR-139 |
| Target: | Glut-1 | PHLPP2, PTEN | BCL2 | EOMES, perforin | EOMES, perforin |
| miRNAs: | miR-28 | miR-138 | Let-7 | miR-181a | |
| Target: | CTLA-4, PD-1 | CTLA-4, PD-1 | CCR2, CCR5 | DUSP5, DUSP6, PTPN11, PTPN22 |
For more miRNA information please contact us.
Support Data
The following are miRNAs introduced into CAR T-cells in some studies.
| miRNAs | Target | CAR T cells | Function |
| miR-155 | SOCS-1 | anti-CD19 CAR T-cells | Enhances trafficking and promotes an effective antitumor response |
| miR-143 | Glut-1 | anti-HER2-CAR T cells | Promote memory T cell development |
| miR-17-92 | PHLPP2, PTEN | anti-EGFRvIII CAR T-cells | Enhance cell proliferation, persistence, and differentiation |
Reference
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