儿童高危神经母细胞瘤免疫治疗进展

李杰; 龚宝成; 李龙

doi:10.12354/j.issn.1000-8179.2023.20221687

儿童高危神经母细胞瘤免疫治疗进展

doi: 10.12354/j.issn.1000-8179.2023.20221687

李杰^1,,
龚宝成¹,
李龙^{1, 2, ,}

1.
天津医科大学肿瘤医院儿童肿瘤科，国家恶性肿瘤临床研究中心，天津市“肿瘤防治”重点实验室，天津市恶性肿瘤临床医学研究中心（天津市300060）
2.
天津医科大学基础医学院免疫学系

详细信息

作者简介:
李杰：专业方向为儿童实体瘤临床治疗

通讯作者:
李龙　Long.Li@tmu.edu.cn

计量
- 文章访问数: 52
- HTML全文浏览量: 5
- PDF下载量: 17
- 被引次数: 0
出版历程
- 收稿日期: 2022-12-06
- 录用日期: 2023-02-09
- 修回日期: 2023-02-08

Advances in immunotherapy for high-risk neuroblastoma in children

Jie Li^1
,,
Baocheng Gong¹,
Long Li^{1, 2
, ,}

1.
Department of Pediatric Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention & Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
2.
Department of Immunology, School of Basic Medicine, Tianjin Medical University, Tianjin 300070, China

More Information

Corresponding author: Long Li; E-mail: 736552942@qq.com

摘要

摘要: 神经母细胞瘤（neuroblastoma，NB）是儿童最常见的颅外实体瘤，具有明显的异质性及独特而多变的生物学和临床特征。高危NB属于免疫学“冷肿瘤”，具有多方位的免疫逃避策略，众多研究者针对这些免疫逃避策略开展了一系列免疫治疗相关探索。目前双唾液酸神经节苷脂（GD2）单抗治疗已被纳入国内外NB多模式治疗共识。尽管如此，高危NB患儿5年生存率仍然低于50%。针对高危NB细胞及其免疫微环境中各种效应分子的免疫治疗研究正在持续进行中，有望为此类患儿带来新希望。本文对目前高危NB患儿采用的免疫治疗方法和研究中的免疫治疗策略进行综述。
- 神经母细胞瘤 /
- 免疫治疗 /
- 抗体治疗 /
- 细胞治疗 /
- 肿瘤疫苗
Abstract: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. It has obvious heterogeneity and unique biological features. High-risk NB is recognized as a "cold tumor" in immunity. It has multidimensional immune evasion strategies. Based on these immune evasion strategies, researchers have performed a series of immunotherapy researches. Although, GD2 mono-antibodies based treatment has been included in the multi-modal treatment around the world, the 5-year survival rate of high-risk NB is still less than 50%. Immunotherapy studies targeting various effector molecules in high-risk NB cells and their immune microenvironment are being explored. These studies are expected to bring new hope to patients with high-risk NB. This article reviews the immunotherapy methods and the immunotherapy strategies in the research of high-risk NB patients.
- neuroblastoma (NB) /
- immunotherapy /
- antibody therapy /
- cellular therapy /
- tumor vaccine

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参考文献(35)

[1]	Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12(4):252-264. doi: 10.1038/nrc3239
[2]	Ackermann S, Cartolano M, Hero B, et al. A mechanistic classification of clinical phenotypes in neuroblastoma[J]. Science, 2018, 362(6419):1165-1170. doi: 10.1126/science.aat6768
[3]	Rossor T, Khakoo Y, et al. Diagnosis and management of opsoclonus-myoclonus-Ataxia syndrome in children: an international perspective[J]. Neurol Neuroimmunol Neuroinflamm, 2022, 9(3):e1153.
[4]	Wienke J, Dierselhuis MP, Tytgat GAM, et al. The immune landscape of neuroblastoma: challenges and opportunities for novel therapeutic strategies in pediatric oncology[J]. Eur J Cancer, 2021, 144:123-150. doi: 10.1016/j.ejca.2020.11.014
[5]	Qiu B, Matthay KK. Advancing therapy for neuroblastoma[J]. Nat Rev Clin Oncol, 2022, 19(8):515-533. doi: 10.1038/s41571-022-00643-z
[6]	Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma[J]. N Engl J Med, 2010, 363(14):1324-1334. doi: 10.1056/NEJMoa0911123
[7]	Ladenstein R, Pötschger U, Valteau-Couanet D, et al. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial[J]. Lancet Oncol, 2018, 19(12):1617-1629.
[8]	Codarri Deak L, Nicolini V, Hashimoto M, et al. PD-1-cis IL-2R agonism yields better effectors from stem-like CD8⁺T cells[J]. Nature, 2022, 610(7930):161-172. doi: 10.1038/s41586-022-05192-0
[9]	Stagno MJ, Schmidt A, Bochem J, et al. Epitope detection in monocytes (EDIM) for liquid biopsy including identification of GD2 in childhood neuroblastoma-a pilot study[J]. Br J Cancer, 2022, 127(7):1324-1331.
[10]	Chan GCF, Chan CM. Anti-GD2 directed immunotherapy for high-risk and metastatic neuroblastoma[J]. Biomolecules, 2022, 12(3):358.
[11]	Zhao B, Li H, Xia Y, et al. Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy[J]. J Hematol Oncol, 2022, 15(1):153. doi: 10.1186/s13045-022-01364-7
[12]	Carpenter EL, Mossé YP. Targeting ALK in neuroblastoma: preclinical and clinical advancements[J]. Nat Rev Clin Oncol, 2012, 9(7):391-399.
[13]	Weidle UH, Eggle D, Klostermann S. L1-CAM as a target for treatment of cancer with monoclonal antibodies[J]. Anticancer Res, 2009, 29(12):4919-4931.
[14]	Wachowiak R, Fiegel HC, Kaifi JT, et al. L1 is associated with favorable outcome in neuroblastomas in contrast to adult tumors[J]. Ann Surg Oncol, 2007, 14(12):3575-3580. doi: 10.1245/s10434-007-9608-0
[15]	Furman WL, McCarville B, Shulkin BL, et al. Improved outcome in children with newly diagnosed high-risk neuroblastoma treated with chemoimmunotherapy: updated results of a phase II study using hu14.18K322A[J]. J Clin Oncol, 2022, 40(4):335-344.
[16]	Fleurence J, Fougeray S, Bahri M, et al. Targeting O-acetyl-GD2 ganglioside for cancer immunotherapy[J]. J Immunol Res, 2017, 5:5604891.
[17]	Su YD, Luo BY, Lu Y, et al. Anlotinib induces a T cell-inflamed tumor microenvironment by facilitating vessel normalization and enhances the efficacy of PD-1 checkpoint blockade in neuroblastoma[J]. Clin Cancer Res, 2022, 28(4):793-809.
[18]	Mody R, Naranjo A, Van Ryn C, et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial[J]. Lancet Oncol, 2017, 18(7):946-957. doi: 10.1016/S1470-2045(17)30355-8
[19]	Mody R, Yu AL, Naranjo A, et al. Irinotecan, temozolomide, and dinutuximab with GM-CSF in children with refractory or relapsed neuroblastoma: a report from the children’s oncology group[J]. J Clin Oncol, 2020, 38(19):2160-2169. doi: 10.1200/JCO.20.00203
[20]	Furman WL, Federico SM, Mccarville MB, et al. A phase Ⅱ trial of hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma[J]. Clinical Cancer Research, 2019, 25(21):6320-6328. doi: 10.1158/1078-0432.CCR-19-1452
[21]	Wang YP, Gao WQ, Shi XY, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin[J]. Nature, 2017, 547(7661):99-103. doi: 10.1038/nature22393
[22]	Luo BY, Wang LM, Gao WJ, et al. Using a gene network of pyroptosis to quantify the responses to immunotherapy and prognosis for neuroblastoma patients[J]. Front Immunol, 2022, 13:845757. doi: 10.3389/fimmu.2022.845757
[23]	Cheung NK, Kushner BH, LaQuaglia M, et al. N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age[J]. Med Pediatr Oncol, 2001, 36(1):227-230. doi: 10.1002/1096-911X(20010101)36:1<227::AID-MPO1055>3.0.CO;2-U
[24]	Bailey K, Pandit-Taskar N, Humm JL, et al. Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes[J]. J Neurooncol, 2019, 143(1):101-106. doi: 10.1007/s11060-019-03139-6
[25]	Toews K, Grunewald L, Schwiebert S, et al. Central memory phenotype drives success of checkpoint inhibition in combination with CAR T cells[J]. Mol Carcinog, 2020, 59(7):724-735. doi: 10.1002/mc.23202
[26]	Chen YH, Sun C, Landoni E, et al. Eradication of neuroblastoma by T cells redirected with an optimized GD2-specific chimeric antigen receptor and interleukin-15[J]. Clin Cancer Res, 2019, 25(9):2915-2924. doi: 10.1158/1078-0432.CCR-18-1811
[27]	Moghimi B, Muthugounder S, Jambon S, et al. Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma[J]. Nat Commun, 2021, 12(1):511. doi: 10.1038/s41467-020-20785-x
[28]	Tian M, Cheuk AT, Wei JS, et al. An optimized bicistronic chimeric antigen receptor against GPC2 or CD276 overcomes heterogeneous expression in neuroblastoma[J]. J Clin Invest, 2022, 132(16):e155621.
[29]	Castriconi R, Dondero A, Cilli M, et al. Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice[J]. Cancer Immunol Immunother, 2007, 56(11):1733-1742.
[30]	Liu Y, Wu HW, Sheard MA, et al. Growth and activation of natural killer cells Ex vivo from children with neuroblastoma for adoptive cell therapy[J]. Clin Cancer Res, 2013, 19(8):2132-2143. doi: 10.1158/1078-0432.CCR-12-1243
[31]	Nguyen R, Sahr N, Sykes A, et al. Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial[J]. J Immunother Cancer, 2020, 8(1):e000176. doi: 10.1136/jitc-2019-000176
[32]	Metelitsa LS. Anti-tumor potential of type-I NKT cells against CD1d-positive and CD1d-negative tumors in humans[J]. Clin Immunol, 2011, 140(2):119-129. doi: 10.1016/j.clim.2010.10.005
[33]	Heczey A, Liu DF, Tian GW, et al. Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy[J]. Blood, 2014, 124(18):2824-2833. doi: 10.1182/blood-2013-11-541235
[34]	Croce M, Meazza R, Orengo AM, et al. Immunotherapy of neuroblastoma by an Interleukin-21-secreting cell vaccine involves survivin as antigen[J]. Cancer Immunol Immunother, 2008, 57(11):1625-1634.
[35]	Temizoz B, Kuroda E, Ishii KJ. Vaccine adjuvants as potential cancer immunotherapeutics[J]. Int Immunol, 2016, 28(7):329-338. doi: 10.1093/intimm/dxw015