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journal article·2025-06Open access

IL‐21 Loading CaMnCO 3 Vitality Backpacks Boost CAR‐T Cell Synergistic Immunotherapy

Baihui Wang, Yuchan Xue, Yang Jia, Yuyao Duan, Dejun Li, Minghao Sui, Yuemin Feng, Le Wang, Han Ding, Xinyu Wang, Tianru Zhang, Yanning Sun, Huimin Liu, Jianni Qi, Jiazhi Duan, Songbo Zhao, Qiang Zhu

Small· Volume 21· Issue 25
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Abstract

Abstract Chimeric antigen receptor (CAR)‐T‐cell therapy achieves considerable success in the treatment of malignant tumors, but clinical relapse due to the tumor microenvironment (TME) is very common. The TME of solid tumors is characterized by weak acidity, hypoxia, and elevated reactive oxygen species (ROS) levels, which collectively impair the function and persistence of infiltrating CAR‐T cells. In this study, acid‐sensitive responsive CaMnCO 3 nanoparticles (CMC NPs), are developed that simultaneously mitigate TME acidosis and hypoxia. IL‐21 is encapsulated within CMC NPs (denoted as CMC‐21), which are then surface‐conjugated to CAR‐T cells as functional ‘vitality backpacks’ to enhance cellular activity. The CMC‐21 backpack enables sustained release of IL‐21, persistently enhancing CAR‐T cell antitumor immunity across both low‐ and high‐dose infusion regimens. Furthermore, CMC NPs exert dual modulatory effects on the TME by: 1) consuming protons to neutralize acidic conditions, and 2) catalytically converting endogenous H 2 O 2 to O 2 to relieve hypoxia. This multimodal remodeling of the immunosuppressive TME significantly enhances the infiltration and activity of adoptively transferred CAR‐T cells while simultaneously boosting endogenous T cell and NK cell recruitment in vivo. These findings establish a novel CAR‐T cell enhancement strategy through sustained IL‐21 release from CMC‐21 backpacks, offering new possibilities for solid tumor immunotherapy.
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Research context

NanomaterialsCatalysis & surfaces

OpenAlex topics: CAR-T cell therapy research · Nanowire Synthesis and Applications · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 P. R. China

Department of Gastroenterology Qilu Hospital (Qingdao) Cheeloo College of Medicine Shandong University Qingdao Shandong 266001 P. R. China

Department of Thoracic Surgery Shandong Provincial Hospital affiliated to Shandong First Medical University Jinan Shandong 250021 P. R. China

Reproductive Medical Center The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan Shandong 250012 P. R. China

Department of ICU Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 P. R. China

Urology Department Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan Shandong 250021 P. R. China

Department of Central Laboratory Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 P. R. China

Institute for Advanced Interdisciplinary Research University of Jinan Jinan 250022 P. R. China

Department of Infectious Disease Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 P. R. China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shandong Province

References (51)

Show source-provided references
1. 10.1038/s41408-021-00459-710.1038/s41408-021-00459-7 ↗
2. 10.1016/j.jhep.2023.01.01110.1016/j.jhep.2023.01.011 ↗
3. 10.3389/fimmu.2023.117268110.3389/fimmu.2023.1172681 ↗
4. 10.1016/j.jcis.2025.01.14910.1016/j.jcis.2025.01.149 ↗
5. 10.1016/j.compositesb.2021.10936410.1016/j.compositesb.2021.109364 ↗
6. 10.1016/j.cell.2020.11.00910.1016/j.cell.2020.11.009 ↗
7. 10.1038/s41467-022-33968-510.1038/s41467-022-33968-5 ↗
8. 10.1021/acsnano.9b1003710.1021/acsnano.9b10037 ↗
9. 10.1016/j.bioactmat.2023.10.02310.1016/j.bioactmat.2023.10.023 ↗
10. 10.1186/s13045-017-0548-210.1186/s13045-017-0548-2 ↗
11. 10.1016/j.canlet.2014.12.04710.1016/j.canlet.2014.12.047 ↗
12. 10.1007/s12032-023-02051-410.1007/s12032-023-02051-4 ↗
13. 10.1172/jci.insight.13200010.1172/jci.insight.132000 ↗
14. 10.1021/acs.accounts.9b0014810.1021/acs.accounts.9b00148 ↗
15. 10.1016/j.actbio.2020.04.01510.1016/j.actbio.2020.04.015 ↗
16. 10.1021/acsnano.3c0121510.1021/acsnano.3c01215 ↗
17. 10.34133/bmr.002810.34133/bmr.0028 ↗
18. 10.1016/j.jcis.2023.05.09910.1016/j.jcis.2023.05.099 ↗
19. 10.1016/j.jcis.2023.04.04910.1016/j.jcis.2023.04.049 ↗
20. 10.1002/adhm.20230396310.1002/adhm.202303963 ↗
21. 10.1021/acs.chemmater.6b0506210.1021/acs.chemmater.6b05062 ↗
22. 10.1021/jacs.7b1103610.1021/jacs.7b11036 ↗
23. 10.1016/j.molcel.2017.05.02810.1016/j.molcel.2017.05.028 ↗
24. 10.1016/j.ijbiomac.2021.10.01410.1016/j.ijbiomac.2021.10.014 ↗
25. 10.1021/acsnano.4c0869010.1021/acsnano.4c08690 ↗
26. 10.1038/s41419-020-03256-510.1038/s41419-020-03256-5 ↗
27. 10.1021/acs.nanolett.0c0477810.1021/acs.nanolett.0c04778 ↗
28. 10.1021/acsnano.0c0388110.1021/acsnano.0c03881 ↗
29. 10.1016/j.bioactmat.2023.11.01710.1016/j.bioactmat.2023.11.017 ↗
30. 10.1016/j.tibs.2007.01.00310.1016/j.tibs.2007.01.003 ↗
31. 10.1016/j.molcel.2012.10.02310.1016/j.molcel.2012.10.023 ↗
32. 10.1126/scitranslmed.aaf363410.1126/scitranslmed.aaf3634 ↗
33. 10.1002/hep.3265810.1002/hep.32658 ↗
34. 10.1016/S0959-437X(00)00156-810.1016/S0959-437X(00)00156-8 ↗
35. 10.1007/s10565-023-09821-w10.1007/s10565-023-09821-w ↗
36. 10.1016/j.ymthe.2023.01.00210.1016/j.ymthe.2023.01.002 ↗
37. 10.2147/IJN.S23505810.2147/IJN.S235058 ↗
38. 10.1016/j.omton.2024.20081710.1016/j.omton.2024.200817 ↗
39. 10.1021/acsami.1c0043010.1021/acsami.1c00430 ↗
40. 10.1093/jnci/djy13110.1093/jnci/djy131 ↗
41. 10.1002/adma.20210652010.1002/adma.202106520 ↗
42. 10.1056/NEJMoa110384910.1056/NEJMoa1103849 ↗
43. 10.1111/j.1600-065X.1997.tb00978.x10.1111/j.1600-065X.1997.tb00978.x ↗
44. 10.1016/j.biomaterials.2021.12134110.1016/j.biomaterials.2021.121341 ↗
45. 10.1179/joc.2007.19.5.56210.1179/joc.2007.19.5.562 ↗
46. 10.1158/1078-0432.CCR-18-038110.1158/1078-0432.CCR-18-0381 ↗
47. 10.1038/nm.383810.1038/nm.3838 ↗
48. 10.1186/s40824-023-00369-810.1186/s40824-023-00369-8 ↗
49. 10.34133/bmr.002310.34133/bmr.0023 ↗
50. 10.1136/jitc-2021-00317610.1136/jitc-2021-003176 ↗
51. 10.1172/jci.insight.9904810.1172/jci.insight.99048 ↗