Professor Yiran Zheng's group develops a novel chemokine-based navigation system for enhancing the efficacy of CAR-T cell therapies against solid tumors

Chimeric antigen receptor T cell (CAR-T cell) therapy is one of the most cutting-edge and potent cancer treatment strategies. However, the efficacy of CAR-T cells is still mediocre for solid tumors. The main limiting factors include low number of intra-tumoral CAR-T cells. Systemically infused CAR-T cells need to traffic to tumor sites and infiltrate tumor before encountering and eradicating tumor cells. Unfortunately, only ~5% of injected CAR-T cells could reach tumor sites. Promoting the tumor-specific migration of CAR-T cells can substantially improve their frequency of CAR-T cells in tumor.

 Recently, Professor Yiran Zheng published a research paper as a cover article titled Chemokine-based Injectable Navigation System for Enhanced CAR-T Cell Therapy Targeting Solid Tumors in Advanced Functional Materials.

This study presents a novel chemokine-based navigation system (CITE) that offers precise tumor navigation and intelligent CAR-T cell arming functions.The migration of CAR-T cells relies on concentration gradients of chemokines. The CITE system includes an immunogel designed for efficiently co-loading chemokine CXCL9 and PD-1 targeting antibody (aPD1). After injection, CITE can functions as a drug depot to continuously release loaded CXCL9 and aPD1. On the other hand, the iRGD peptide co-administered with CAR-T cells in the CITE system can enhance the tumor infiltration of CXCL9 and aPD1. The significantly increased concentration of CXCL9 and aPD1 in tumor substantially improved the tumor-specific migration and tumor-killing ability of CAR-T cells. The CITE system increased T cell infiltration into tumors by more than 200 times, making it an effective treatment for immunological cold breast cancer. Furthermore, CITE has the ability to elicit immunological abscopal effects and immune memory for treating systemic tumors and preventing recurrence.CITE is broadly applicable in improving adoptive T cell therapies involving CAR-T cells, TCR-T cells or TIL.

       Wenjun Wan, a PhD student, and Wenqing Han, a former master student at our college, are the co-first authors of this study. Professor Yiran Zheng is the corresponding author.This study was supported by the National Natural Science Foundation of China (82150410455), “Open Competition to Select the Best Candidates”Key Technology Program for Cell Therapy of NCTIB (NCTIB2023XB02012), Interdisciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow University and Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

Reference:

Wenjun Wan, Wenqing Han, J. Chen, Y.J. Li, L. Zhao, M.Q. Gao, C. Shen, N. Liu, W.H. Deng, S.Q. Ma, L.F. Cheng, Yiran Zheng*, Chemokine-based injectable navigation system for enhancing CAR-T cell therapy against solid tumors, Advanced Functional Materials 2024, 2401161.

Full-text link:https://doi.org/10.1002/adfm.202401161

Corresponding author:

Yiran Zheng is a professor at the College of Pharmaceutical Sciences, Soochow University. Zheng’s laboratory has focused on immuno-engineering to tailor immune responses for enhanced CAR-T cell therapies and vaccines. In recent years, he has published academic papers as first or corresponding author in journals including Nat Biotechnol, Adv Mater, ACS Nano, Adv Funct Mater, J Control Release. To date, Prof Zheng’s papers have been cited for more than 3000 times. He also has 5 granted patents with 3 licensed to biopharmaceutical companies. Company product based on the relevant technologies undergoes phase I clinical trial in USA.