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

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11:69.

Article  PubMed  PubMed Central  Google Scholar 

Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer. 2021;21:145–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henke E, Nandigama R, Ergün S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front Mol Biosci. 2020;6:160.

Article  PubMed  PubMed Central  Google Scholar 

Cheever A, Townsend M, O’Neill K. Tumor microenvironment immunosuppression: a roadblock to CAR T-cell advancement in solid tumors. Cells. 2022;11:3626.

Article  Google Scholar 

Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L. Macrophages and metabolism in the tumor microenvironment. Cell Metab. 2019;30:36–50.

Article  CAS  PubMed  Google Scholar 

Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383:2255–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Yeku OO, Longo DL. CAR T cells for neuroblastoma. N Engl J Med. 2023;388:1328–31.

Article  CAS  PubMed  Google Scholar 

Furman WL. Monoclonal antibody therapies for high risk neuroblastoma. Biologics. 2021;15:205–19.

PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wienke J, Dierselhuis MP, Tytgat GAM, Künkele 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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif