CAR‐Aptamers Enable Traceless Enrichment and Monitoring of CAR‐Positive Cells and Overcome Tumor Immune Escape

• Published in: Advanced science Vol. 11; no. 10; pp. e2305566 - n/a
• Main Authors: Zhou, Hang, Abudureheman, Tuersunayi, Zheng, Wei‐Wei, Yang, Li‐Ting, Zhu, Jian‐Min, Liang, Ai‐Bin, Duan, Cai‐Wen, Chen, Kaiming
• Format: Journal Article
• Language: English
• Published: Germany John Wiley and Sons Inc 01.03.2024; Wiley
• Subjects: aptamers; CAR‐T cells; monitor; retargeting; traceless enrichment; monitor; retargeting; aptamers; CAR-T cells; traceless enrichment
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202305566

Chimeric antigen receptor (CAR)‐positive cell therapy, specifically with anti‐CD19 CAR‐T (CAR19‐T) cells, achieves a high complete response during tumor treatment for hematological malignancies. Large‐scale production and application of CAR‐T therapy can be achieved by developing efficient and low‐cost enrichment methods for CAR‐T cells, expansion monitoring in vivo, and overcoming tumor escape. Here, novel CAR‐specific binding aptamers (CAR‐ap) to traceless sort CAR‐positive cells and obtain a high positive rate of CAR19‐T cells is identified. Additionally, CAR‐ap‐enriched CAR19‐T cells exhibit similar antitumor capacity as CAR‐ab (anti‐CAR antibody)‐enriched CAR‐T cells. Moreover, CAR‐ap accurately monitors the expansion of CAR19‐T cells in vivo and predicts the prognosis of CAR‐T treatment. Essentially, a novel class of stable CAR‐ap‐based bispecific circular aptamers (CAR‐bc‐ap) is constructed by linking CAR‐ap with a tumor surface antigen (TSA): protein tyrosine kinase 7 (PTK7) binding aptamer Sgc8. These CAR‐bc‐aps significantly enhance antitumor cytotoxicity with a loss of target antigens by retargeting CAR‐T cells to the tumor in vitro and in vivo. Overall, novel CAR‐aptamers are screened for traceless enrichment, monitoring of CAR‐positive cells, and overcoming tumor cell immune escape. This provides a low‐cost and high‐throughput approach for CAR‐positive cell‐based immunotherapy. a) The concept illustration of the CAR‐ap aptamer SELEX process. b) CAR‐ap aptamers used for traceless enrichment of CAR19‐T cells. c) CAR‐ap can specifically monitor CAR‐positive cells. d) CAR‐ap aptamers retarget CAR19‐T cells to CD19 antigen‐lost tumor cells.