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Tumor cell membrane remodeling with universal ligand for CAR-T cells to inhibit solid tumors

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Abstract

Heterogeneity is a major obstacle to the success of CAR-T therapy in treating solid tumors. The complex tumor microenvironment and varying phenotypes of tumor cells might result in antigen escape, drug resistance, and tumor recurrence. To address this issue, we proposed to use lipid-modified fluorescein isothiocyanate (Lip-FITC) as an artificial ligand to normalize the phenotypes of solid tumor cells. In murine cutaneous melanoma and colon adenocarcinoma that prefer to utilize exogenous long-chain fatty acids, we observed much more uptake of Lip-FITC and significantly increased FITC fluorescence on tumor cell membranes than normal cells. This specific exogenous labeling with FITC enhanced the recognition and selectivity of CART cells in solid tumors, bypassing the limitations derived from antigen expression differences in adoptive cell therapies. Lipid metabolism analysis and in vitro experiments demonstrated the sufficient uptake of long-chain fatty acid (LCFAs)-modified Lip-FITC by solid tumor cells, as well as satisfactory ligand assembly on cell membranes. In solid tumor model, the treatment induced the recognition and initiation of CART cells and successfully suppressed tumor progression through T-cell immunity.

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References

  1. Agarwalla P, Ogunnaike EA, Ahn S, Froehlich KA, Jansson A, Ligler FS, Dotti G, Brudno Y. Nat Biotechnol, 2022, 40: 1250–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Maalej KM, Merhi M, Inchakalody VP, Mestiri S, Alam M, Maccalli C, Cherif H, Uddin S, Steinhoff M, Marincola FM, Dermime S. Mol Cancer, 2023, 22: 20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Abreu TR, Fonseca NA, Gonçalves N, Moreira JN. J Control Release, 2020, 319: 246–261

    Article  CAS  PubMed  Google Scholar 

  4. Cheng EL, Cardle II, Kacherovsky N, Bansia H, Wang T, Zhou Y, Raman J, Yen A, Gutierrez D, Salipante SJ, des Georges A, Jensen MC, Pun SH. J Am Chem Soc, 2022, 144: 13851–13864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gao F, Cheng Q, Liu MD, Rong L, Liu CJ, Zhang XZ. Sci China Chem, 2019, 62: 1230–1244

    Article  CAS  Google Scholar 

  6. Hong M, Clubb JD, Chen YY. Cancer Cell, 2020, 38: 473–488

    Article  CAS  PubMed  Google Scholar 

  7. Nie W, Fan W, Jiang A, Wu G, Liu H, Huang LL, Xie HY. Sci China Chem, 2021, 64: 1999–2009

    Article  CAS  Google Scholar 

  8. Liu G, Rui W, Zhao X, Lin X. Cell Mol Immunol, 2021, 18: 1085–1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen Q, Hu Q, Dukhovlinova E, Chen G, Ahn S, Wang C, Ogunnaike EA, Ligler FS, Dotti G, Gu Z. Adv Mater, 2019, 31: e1900192

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hong S, Huang QX, Zhong Z, Rong L, Zhang XZ. CCS Chem, 2022, 4: 1770–1787

    Article  CAS  Google Scholar 

  11. Zhang AQ, Hostetler A, Chen LE, Mukkamala V, Abraham W, Padilla LT, Wolff AN, Maiorino L, Backlund CM, Aung A, Melo M, Li N, Wu S, Irvine DJ. Nat Biomed Eng, 2023, doi: https://doi.org/10.1038/s41551-023-01048-8

  12. Zhang M, Di Martino JS, Bowman RL, Campbell NR, Baksh SC, Simon-Vermot T, Kim IS, Haldeman P, Mondal C, Yong-Gonzales V, Abu-Akeel M, Merghoub T, Jones DR, Zhu XG, Arora A, Ariyan CE, Birsoy K, Wolchok JD, Panageas KS, Hollmann T, Bravo-Cordero JJ, White RM. Cancer Discov, 2018, 8: 1006–1025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wen D, Wang J, Van Den Driessche G, Chen Q, Zhang Y, Chen G, Li H, Soto J, Liu M, Ohashi M, Wang Z, Abdou P, Hu Q, Dotti G, Li S, Fourches D, Gu Z. Matter, 2019, 1: 1203–1214

    Article  Google Scholar 

  14. Wang YY, Attané C, Milhas D, Dirat B, Dauvillier S, Guerard A, Gilhodes J, Lazar I, Alet N, Laurent V, Le Gonidec S, Biard D, Hervé C, Bost F, Ren GS, Bono F, Escourrou G, Prentki M, Nieto L, Valet P, Muller C. JCI Insight, 2017, 2: e87489

    PubMed  PubMed Central  Google Scholar 

  15. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB, Rabinowitz JD. Proc Natl Acad Sci USA, 2013, 110: 8882–8887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Koonen DPY, Glatz JFC, Bonen A, Luiken JJFP. Biochim Biophys Acta, 2005, 1736: 163–180

    Article  CAS  PubMed  Google Scholar 

  17. Liang T, Wen D, Chen G, Chan A, Chen Z, Li H, Wang Z, Han X, Jiang L, Zhu JJ, Gu Z. Adv Mater, 2021, 33: e2100629

    Article  PubMed  Google Scholar 

  18. Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC, Martin-Sandoval MS, Gu Z, McCormick ML, Durham AB, Spitz DR, Zhao Z, Mathews TP, Morrison SJ. Nature, 2020, 585: 113–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Olzmann JA, Carvalho P. Nat Rev Mol Cell Biol, 2019, 20: 137–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang J, Hao JW, Wang X, Guo H, Sun HH, Lai XY, Liu LY, Zhu M, Wang HY, Li YF, Yu LY, Xie C, Wang HR, Mo W, Zhou HM, Chen S, Liang G, Zhao TJ. Cell Rep, 2019, 26: 209–221.e5

    Article  PubMed  Google Scholar 

  21. van Meer G, Voelker DR, Feigenson GW. Nat Rev Mol Cell Biol, 2008, 9: 112–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Phillips MJ, Voeltz GK. Nat Rev Mol Cell Biol, 2016, 17: 69–82

    Article  CAS  PubMed  Google Scholar 

  23. Wang B, Tontonoz P. Annu Rev Physiol, 2019, 81: 165–188

    Article  PubMed  Google Scholar 

  24. Zheng Y, Nandakumar KS, Cheng K. J Med Chem, 2021, 64: 9577–9591

    Article  CAS  PubMed  Google Scholar 

  25. Zhang B, Wang Y, Huang S, Sun J, Wang M, Ma W, You Y, Wu L, Hu J, Song W, Liu X, Li S, Chen H, Zhang G, Zhang L, Zhou D, Li L, Zhang X. Cell Chem Biol, 2021, 28: 60–69.e7

    Article  CAS  PubMed  Google Scholar 

  26. Fan JX, Liu XH, Wang XN, Niu MT, Chen QW, Zheng DW, Wei JS, Yang XQ, Zeng X, Zhang XZ. Adv Funct Mater, 2021, 31: 2009744

    Article  CAS  Google Scholar 

  27. Hong S, Huang QX, Ji P, Pang X, Sun Y, Cheng SX, Zhang XZ, Chen X. Sci China Chem, 2022, 65: 1994–2004

    Article  CAS  Google Scholar 

  28. Bi J, Ichu TA, Zanca C, Yang H, Zhang W, Gu Y, Chowdhry S, Reed A, Ikegami S, Turner KM, Zhang W, Villa GR, Wu S, Quehenberger O, Yong WH, Kornblum HI, Rich JN, Cloughesy TF, Cavenee WK, Furnari FB, Cravatt BF, Mischel PS. Cell Metab, 2019, 30: 525–538.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yin J, Pidgeon C. Tetrahedron Lett, 1997, 38: 5953–5954

    Article  CAS  Google Scholar 

  30. Liu M, Xu W, Xu LJ, Zhong GR, Chen SL, Lu WY. Chem, 2005, 16: 1126–1132

    CAS  Google Scholar 

  31. Ortiz RA, Flores RVG, García Valdéz AE, Duarte MLB. Prog Org Coat, 2010, 69: 463–469

    Article  CAS  Google Scholar 

  32. Zhang D, Liu C, Chen S, Zhang J, Cheng J, Miao M. Prog Org Coat, 2016, 101: 178–185

    Article  CAS  Google Scholar 

  33. Zhang QL, Zheng D, Dong X, Pan P, Zeng SM, Gao F, Cheng SX, Zhang XZ. J Am Chem Soc, 2021, 143: 5127–5140

    Article  CAS  PubMed  Google Scholar 

  34. Ma X, Liang X, Li Y, Feng Q, Cheng K, Ma N, Zhu F, Guo X, Yue Y, Liu G, Zhang T, Liang J, Ren L, Zhao X, Nie G. Nat Commun, 2023, 14: 1606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sockolosky JT, Dougan M, Ingram JR, Ho CCM, Kauke MJ, Almo SC, Ploegh HL, Garcia KC. Proc Natl Acad Sci USA, 2016, 113: E2646–E2654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fan JX, Peng MY, Wang H, Zheng HR, Liu ZL, Li CX, Wang XN, Liu XH, Cheng SX, Zhang XZ. Adv Mater, 2019, 31: e1808278

    Article  PubMed  Google Scholar 

  37. Jiang H, Guo Y, Yu Z, Hu P, Shi J. Natl Sci Rev, 2022, 9: nwac169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen WH, Chen QW, Chen Q, Cui C, Duan S, Kang Y, Liu Y, Liu Y, Muhammad W, Shao S, Tang C, Wang J, Wang L, Xiong MH, Yin L, Zhang K, Zhang Z, Zhen X, Feng J, Gao C, Gu Z, He C, Ji J, Jiang X, Liu W, Liu Z, Peng H, Shen Y, Shi L, Sun X, Wang H, Wang J, Xiao H, Xu FJ, Zhong Z, Zhang XZ, Chen X. Sci China Chem, 2022, 65: 1010–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wu Y, Wen H, Bernstein ZJ, Hainline KM, Blakney TS, Congdon KL, Snyder DJ, Sampson JH, Sanchez-Perez L, Collier JH. Sci Adv, 2022, 8: eabm7833

    Google Scholar 

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Acknowledgements This work was supported by the National Natural Science Foundation of China (52103319, 22135005, 51988102). All of the animal experiments were conducted under protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the Animal Experiment Center of Wuhan University (Wuhan, China).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, China

    Jin-Xuan Fan, Wen Li & Xian-Zheng Zhang

  2. Department of Orthopedic Trauma and Microsurgery, ZhongNan Hospital of Wuhan University, Wuhan, 430071, China

    Zhong-Bao Hu, Hui-Yun Gu, Wen-Qiang Qu, Bai-Wen Qi, Ai-Xi Yu & Xian-Zheng Zhang

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  1. Jin-Xuan Fan
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  2. Zhong-Bao Hu
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Correspondence to Ai-Xi Yu or Xian-Zheng Zhang.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Fan, JX., Hu, ZB., Gu, HY. et al. Tumor cell membrane remodeling with universal ligand for CAR-T cells to inhibit solid tumors. Sci. China Chem. 66, 3223–3231 (2023). https://doi.org/10.1007/s11426-023-1796-0

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  • DOI: https://doi.org/10.1007/s11426-023-1796-0

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