OpenLB
Open Library of Bioscience
Advanced Search
World journal of pediatrics : WJP
Feb, 2025;21 (2): 123-130.

Challenges and overcoming strategies in CAR-T cell therapy for pediatric neuroblastoma.

Pei-Ting Ying, Yong-Min Tang
Author Information
  1. Pei-Ting Ying: Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, #57 Zhuganxiang Road, Gongshu District, Hangzhou, 310003, China.
  2. Yong-Min Tang: Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, #57 Zhuganxiang Road, Gongshu District, Hangzhou, 310003, China. y_m_tang@zju.edu.cn. ORCID
PMID: 39900866 DOI: 10.1007/s12519-025-00876-9

Abstract

No abstract text available.

References

  1. Ni X, Li Z, Li X, Zhang X, Bai G, Liu Y, et al. Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study. Lancet. 2022;400:1020���32. [PMID: 36154677]
  2. Ayala Ceja M, Khericha M, Harris CM, Puig-Saus C, Chen YY. CAR-T cell manufacturing: major process parameters and next-generation strategies. J Exp Med. 2024;221:e20230903. [PMID: 38226974]
  3. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11:69. [PMID: 33824268]
  4. Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer. 2021;21:145���61. [PMID: 33483715]
  5. Zhang Y, Tacheva-Grigorova SK, Sutton J, Melton Z, Mak YSL, Lay C, et al. Allogeneic CAR T cells targeting DLL3 are efficacious and safe in preclinical models of small cell lung cancer. Clin Cancer Res. 2023;29:971���85. [PMID: 36692420]
  6. Chen T, Wang M, Chen Y, Liu Y. Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors. Cancer Cell Int. 2024;24:133. [PMID: 38622705]
  7. O���Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9:eaaa0984. [PMID: 28724573]
  8. Liu Z, Zhou Z, Dang Q, Xu H, Lv J, Li H, et al. Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy. Theranostics. 2022;12:6273���90. [PMID: 36168626]
  9. Andrea AE, Chiron A, Mallah S, Bessoles S, Sarrabayrouse G, Hacein-Bey-Abina S. Advances in CAR-T cell genetic engineering strategies to overcome hurdles in solid tumors treatment. Front Immunol. 2022;13:830292. [PMID: 35211124]
  10. Henke E, Nandigama R, Erg��n S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front Mol Biosci. 2020;6:160. [PMID: 32118030]
  11. Cheever A, Townsend M, O���Neill K. Tumor microenvironment immunosuppression: a roadblock to CAR T-cell advancement in solid tumors. Cells. 2022;11:3626. [DOI: 10.3390/cells11223626]
  12. Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L. Macrophages and metabolism in the tumor microenvironment. Cell Metab. 2019;30:36���50. [PMID: 31269428]
  13. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383:2255���73. [PMID: 33264547]
  14. Chen X, Li P, Tian B, Kang X. Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors. Front Immunol. 2022;13:1079181. [PMID: 36569917]
  15. Qi C, Liu C, Gong J, Liu D, Wang X, Zhang P, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med. 2024;30:2224���34. [PMID: 38830992]
  16. Rivera Z, Escutia C, Madonna MB, Gupta KH. Biological insight and recent advancement in the treatment of neuroblastoma. Int J Mol Sci. 2023;24:8470. [PMID: 37239815]
  17. Lutskovich D, Meleshko A, Katsin M. State of the art and perspectives of chimeric antigen receptor T cells cell therapy for neuroblastoma. Cytotherapy. 2024;26:1122���31. [PMID: 38852096]
  18. Yeku OO, Longo DL. CAR T cells for neuroblastoma. N Engl J Med. 2023;388:1328���31. [PMID: 37018497]
  19. Furman WL. Monoclonal antibody therapies for high risk neuroblastoma. Biologics. 2021;15:205���19. [PMID: 34135571]
  20. Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, et al. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. N Engl J Med. 2023;388:1284���95. [PMID: 37018492]
  21. Straathof K, Flutter B, Wallace R, Jain N, Loka T, Depani S, et al. Antitumor activity without on-target off-tumor toxicity of GD2���chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020;12:eabd6169. [PMID: 33239386]
  22. Yu L, Huang L, Lin D, Lai X, Wu L, Liao X, et al. GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients. J Cancer Res Clin Oncol. 2022;148:2643���52. [PMID: 34724115]
  23. Kaczanowska S, Murty T, Alimadadi A, Contreras CF, Duault C, Subrahmanyam PB, et al. Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy. Cancer Cell. 2024;42:35���51.e8. [PMID: 38134936]
  24. Heczey A, Louis CU, Savoldo B, Dakhova O, Durett A, Grilley B, et al. CAR T cells administered in combination with lymphodepletion and PD-1 inhibition to patients with neuroblastoma. Mol Ther. 2017;25:2214���24. [PMID: 28602436]
  25. Wienke J, Dierselhuis MP, Tytgat GAM, K��nkele A, Nierkens S, Molenaar JJ. The immune landscape of neuroblastoma: challenges and opportunities for novel therapeutic strategies in pediatric oncology. Eur J Cancer. 2021;144:123���50. [PMID: 33341446]
  26. Zhao B, Li H, Xia Y, Wang Y, Wang Y, Shi Y, et al. Immune checkpoint of B7���H3 in cancer: from immunology to clinical immunotherapy. J Hematol Oncol. 2022;15:153. [PMID: 36284349]
  27. Feng R, Chen Y, Liu Y, Zhou Q, Zhang W. The role of B7���H3 in tumors and its potential in clinical application. Int Immunopharmacol. 2021;101:108153. [PMID: 34678689]
  28. Yang S, Wei W, Zhao Q. B7���H3, a checkpoint molecule, as a target for cancer immunotherapy. Int J Biol Sci. 2020;16:1767���73. [PMID: 32398947]
  29. Majzner RG, Theruvath JL, Nellan A, Heitzeneder S, Cui Y, Mount CW, et al. CAR T cells targeting B7���H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clin Cancer Res. 2019;25:2560���74. [PMID: 30655315]
  30. Du H, Hirabayashi K, Ahn S, Kren NP, Montgomery SA, Wang X, et al. Antitumor responses in the absence of toxicity in solid tumors by targeting B7���H3 via chimeric antigen receptor T cells. Cancer Cell. 2019;35:221���37.e8. [PMID: 30753824]
  31. Nguyen P, Okeke E, Clay M, Haydar D, Justice J, O���Reilly C, et al. Route of 41BB/41BBL costimulation determines effector function of B7���H3-CAR.CD28�� T cells. Mol Ther Oncolytics. 2020;18:202���14. [PMID: 32728609]
  32. Pinto N, Albert CM, Taylor MR, Ullom HB, Wilson AL, Huang W, et al. STRIvE-02: a first-in-human phase I study of systemically administered B7���H3 chimeric antigen receptor T cells for patients with relapsed/refractory solid tumors. J Clin Oncol. 2024;42:4163���72. [PMID: 39255444]
  33. Richards RM, Sotillo E, Majzner RG. CAR T cell therapy for neuroblastoma. Front Immunol. 2018;9:2380. [PMID: 30459759]
  34. Sun M, Cao Y, Okada R, Reyes-Gonz��lez JM, Stack HG, Qin H, et al. Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma. J Immunother Cancer. 2023;11:e005881. [PMID: 36631162]
  35. Heitzeneder S, Bosse KR, Zhu Z, Zhelev D, Majzner RG, Radosevich MT, et al. GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity. Cancer Cell. 2022;40:53���69.e9. [PMID: 34971569]
  36. Bergaggio E, Chiarle R. Impact of ALK inhibitors to potentiate ALK.CAR-T therapy in neuroblastoma. Clin Transl Med. 2024;14:e1732. [PMID: 38877641]
  37. Bergaggio E, Tai WT, Aroldi A, Mecca C, Landoni E, N��esch M, et al. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell. 2023;41:2100���16.e10. [PMID: 38039964]
  38. Park JR, Digiusto DL, Slovak M, Wright C, Naranjo A, Wagner J, et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther. 2007;15:825���33. [PMID: 17299405]
  39. K��nkele A, Taraseviciute A, Finn LS, Johnson AJ, Berger C, Finney O, et al. Preclinical assessment of CD171-directed CAR T-cell adoptive therapy for childhood neuroblastoma: CE7 epitope target safety and product manufacturing feasibility. Clin Cancer Res. 2017;23:466���77. [PMID: 27390347]
  40. Lee JY, Jonus HC, Sadanand A, Branella GM, Maximov V, Suttapitugsakul S, et al. Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma. Cell Rep Med. 2023;4:101091. [PMID: 37343516]
  41. Wu H, Zhang G, Liu Z, Liu W, Wang X, Zhao Y. Enhanced anti-tumor activity mediated by combination chimeric antigen receptor T cells targeting GD2 and GPC2 in high-risk neuroblastoma. Cytotherapy. 2024;26:1308���19. [PMID: 38904586]
  42. Tian M, Cheuk AT, Wei JS, Abdelmaksoud A, Chou HC, Milewski D, et al. An optimized bicistronic chimeric antigen receptor against GPC2 or CD276 overcomes heterogeneous expression in neuroblastoma. J Clin Invest. 2022;132:e155621. [PMID: 35852863]
  43. Halliwell E, Vitali A, Muller H, Alonso-Ferrero M, Barisa M, Gavriil A, et al. Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells. Cytotherapy. 2023;25:46���58. [PMID: 36396552]
  44. Richman SA, Nunez-Cruz S, Moghimi B, Li LZ, Gershenson ZT, Mourelatos Z. High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res. 2018;6:36���46. [PMID: 29180536]
  45. Quintarelli C, Orlando D, Boffa I, Guercio M, Polito VA, Petretto A, et al. Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma. OncoImmunology. 2018;7:e1433518. [PMID: 29872565]
  46. Li G, Zhang Q, Han Z, Zhu Y, Shen H, Liu Z, et al. IL-7 and CCR2b co-expression-mediated enhanced CAR-T survival and infiltration in solid tumors. Front Oncol. 2021;11:734593. [PMID: 34778046]
  47. Chen Y, Sun C, Landoni E, Metelitsa L, Dotti G, Savoldo B. Eradication of neuroblastoma by T cells redirected with an optimized GD2-specific chimeric antigen receptor and interleukin-15. Clin Cancer Res. 2019;25:2915���24. [PMID: 30617136]
  48. Garc��a-Garc��a L, S��nchez E, Ivanova M, Pastora K, Alc��ntara-S��nchez C, Garc��a-Mart��nez J, et al. Choosing T-cell sources determines CAR-T cell activity in neuroblastoma. Front Immunol. 2024;15:1375833. [PMID: 38601159]
  49. Li D, Liang T, Hutchins LE, Wolfarth AA, Ferrando-Martinez S, Lee BH, et al. rhIL-7-hyFc, a long-acting interleukin-7, improves efficacy of CAR-T cell therapy in solid tumors. J Immunother Cancer. 2024;12:e008989. [PMID: 39043602]
  50. Cappabianca D, Pham D, Forsberg MH, Bugel M, Tommasi A, Lauer A, et al. Metabolic priming of GD2 TRAC-CAR T cells during manufacturing promotes memory phenotypes while enhancing persistence. Mol Ther Methods Clin Dev. 2024;32:101249. [PMID: 38699288]
  51. Moghimi B, Muthugounder S, Jambon S, Tibbetts R, Hung L, Bassiri H, et al. Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Nat Commun. 2021;12:511. [PMID: 33479234]
  52. Zhang P, Ying P, Li H, Zhao N, Liu R, Li S, et al. A novel safer CD19CAR with shRNA interference of IFN-�� can reduce multiple cytokine levels without significantly compromising its killing efficacy. Apoptosis. 2024;29:556���67. [PMID: 38114800]
  53. Wang W, Liu Y, He Z, Li L, Liu S, Jiang M, et al. Breakthrough of solid tumor treatment: CAR-NK immunotherapy. Cell Death Discov. 2024;10:40. [PMID: 38245520]
  54. Hadiloo K, Taremi S, Heidari M, Esmaeilzadeh A. The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors. Biomark Res. 2023;11:103. [PMID: 38017494]

Grants

  1. 81470304/National Natural Science Foundation of China
  2. 2019C03032/Medical Science and Technology Project of Zhejiang Province
Editorial

Word Cloud

Created with Highcharts 10.0.0ChallengesovercomingstrategiesCAR-Tcelltherapypediatricneuroblastoma

Similar Articles

Cited By

No available data.