Engineered circular RNA-based DLL3-targeted CAR-T therapy for small cell lung cancer

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 12, 2025

Abstract Purpose Circular RNA (circRNA) has emerged as a promising therapeutic molecule due to its enhanced stability and prolonged protein expression compared messenger (mRNA). Using circRNA construct transient Chimeric Antigen Receptor (CAR)-T cells can mitigate the limitations of conventional viral vector-based CAR-T approaches, such complex process long-term side effects. Methods The study first reconfirmed advantageous properties circRNA, focusing on efficiency. Electroporation conditions were then optimized for efficient delivery into human primary T cells. Subsequently, encoding anti-Delta-like Ligand 3 (DLL3) CAR was constructed, generated via electroporation. efficacy circRNA-based mRNA-based in both vitro vivo models, including subcutaneous orthotopic small cell lung cancer (SCLC) mouse models. Results CircRNA-based demonstrated superior against SCLC In experiments showed tumor-killing effects, while studies revealed complete elimination tumors These results underscored advantages therapy. Conclusions This validated feasibility circRNA-electroporation strategy therapy offered potentially effective approach treating SCLC, highlighting potential technologies advancing therapies. Graphic

Language: Английский

Advancing the next generation of cancer treatment with circular RNAs in CAR-T cell therapy

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117753 - 117753

Published: Dec. 1, 2024

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies. However, its effectiveness against solid tumors remains constrained by challenges such as exhaustion, limited persistence, and off-target effects. These highlight critical gaps in current CAR-T cell therapeutic strategies, particularly for tumor applications. Circular RNAs (circRNAs) represent a transformative class non-coding RNAs, known their exceptional stability precise regulatory functions, positioning them promising candidates enhancing next-generation therapies. Notably, circRNAs can bridge gap between preclinical research clinical application offering innovative solutions to overcome technical hurdles improve outcomes. Despite potential, remain underexplored therapies tumors, presenting significant opportunity innovation. The mechanisms through which modulate specificity are not yet fully understood, challenges, achieving efficient targeted circRNA delivery, still need be addressed. This review highlights importance integrating into enhance specificity, minimize effects, durability. By emphasizing potential identifying key gaps, this provides roadmap advancing setting stage next generation personalized cancer treatments.

Language: Английский