剪接介导的 B 细胞恶性肿瘤免疫治疗中的抗原逃逸。
Splicing-Mediated Antigen Escape from Immunotherapy for B-cell Malignancies.
机构信息
Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
出版信息
Blood Cancer Discov. 2022 Mar 1;3(2):87-89. doi: 10.1158/2643-3230.BCD-21-0200.
Abstract
In this issue of Blood Cancer Discovery, Zheng and colleagues identify that alternative RNA splicing of CD22 within B-cell acute lymphoblastic leukemia can result in antigen escape from CD22-targeted immunotherapies. Drug-resistant isoforms of CD22 exist within leukemic cells pretreatment and can influence response to the CD22-directed antibody-drug conjugate inotuzumab ozogamicin, the immunotoxin moxetumomab pasudotox, as well as anti-CD22 chimeric antigen receptor T cells. See related article by Zheng et al., p. 103 (7).
摘要
在本期《Blood Cancer Discovery》中，Zheng 及其同事确定，B 细胞急性淋巴细胞白血病中 CD22 的选择性 RNA 剪接可导致抗原逃避 CD22 靶向免疫疗法。在白血病细胞预处理时存在 CD22 耐药性同工型，可影响对 CD22 导向抗体药物偶联物伊妥珠单抗奥佐米星、免疫毒素莫昔妥莫单抗帕苏妥昔、以及抗 CD22 嵌合抗原受体 T 细胞的反应。详见 Zheng 等人的相关文章，第 103 页（7）。
相似文献
1
Splicing-Mediated Antigen Escape from Immunotherapy for B-cell Malignancies.剪接介导的 B 细胞恶性肿瘤免疫治疗中的抗原逃逸。
Blood Cancer Discov. 2022 Mar 1;3(2):87-89. doi: 10.1158/2643-3230.BCD-21-0200.
2
Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies.通过广泛的剪接异常调节儿童白血病中的 CD22 蛋白表达：对 CD22 导向免疫治疗的影响。
Blood Cancer Discov. 2022 Mar 1;3(2):103-115. doi: 10.1158/2643-3230.BCD-21-0087.
3
Inotuzumab Ozogamicin: First Pediatric Approval.依妥珠单抗奥佐米星：首款获儿科批准的药物。
Paediatr Drugs. 2024 Jul;26(4):459-467. doi: 10.1007/s40272-024-00634-w. Epub 2024 May 23.
4
Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22.INO-VATE 试验中的伊妥珠单抗奥唑米星治疗复发/难治性急性淋巴细胞白血病：根据基线 CD22 评估 CD22 药效动力学、疗效和安全性
Clin Cancer Res. 2021 May 15;27(10):2742-2754. doi: 10.1158/1078-0432.CCR-20-2399. Epub 2021 Feb 18.
5
Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia.抗CD22免疫毒素莫克妥昔单抗帕苏妥昔用于儿童急性淋巴细胞白血病的1期研究。
Blood. 2017 Oct 5;130(14):1620-1627. doi: 10.1182/blood-2017-02-749101. Epub 2017 Aug 9.
6
Treatment of Recurrent Refractory Pediatric Pre-B Acute Lymphoblastic Leukemia Using Inotuzumab Ozogamicin Monotherapy Resulting in CD22 Antigen Expression Loss as a Mechanism of Therapy Resistance.使用奥英妥珠单抗单药治疗复发性难治性小儿前体B细胞急性淋巴细胞白血病导致CD22抗原表达缺失作为治疗耐药机制
J Pediatr Hematol Oncol. 2019 Nov;41(8):e546-e549. doi: 10.1097/MPH.0000000000001440.
7
Reevaluating Patient Eligibility for Inotuzumab Ozogamicin Based on CD22 Expression: Is Dim Expression Sufficient?基于 CD22 表达重新评估因妥珠单抗奥滨尤妥珠单抗的患者适用性：弱表达是否足够？
Curr Oncol. 2020 Dec 31;28(1):252-259. doi: 10.3390/curroncol28010027.
8
Loss of CD22 expression and expansion of a CD22 subpopulation in adults with relapsed/refractory B-lymphoblastic leukaemia after treatment with Inotuzumab-Ozogamicin.在接受 Inotuzumab-Ozogamicin 治疗后，复发/难治性 B 淋巴细胞白血病成人患者中 CD22 表达缺失和 CD22 亚群扩增。
Ann Hematol. 2021 Nov;100(11):2727-2732. doi: 10.1007/s00277-021-04601-0. Epub 2021 Jul 31.
9
Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia.奥英妥珠单抗用于治疗急性淋巴细胞白血病患者。
Drugs Today (Barc). 2017 Dec;53(12):653-665. doi: 10.1358/dot.2017.53.12.2737934.
10
Inotuzumab ozogamicin compassionate use for French paediatric patients with relapsed or refractory CD22-positive B-cell acute lymphoblastic leukaemia.因诺妥珠单抗奥佐米星在法国复发或难治性CD22阳性B细胞急性淋巴细胞白血病儿科患者中的同情用药。
Br J Haematol. 2020 Jul;190(1):e53-e56. doi: 10.1111/bjh.16732. Epub 2020 May 18.
引用本文的文献
1
Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences.非小细胞肺癌中可变剪接的全基因组分析揭示了新的组织学和人群差异。
Oncogene. 2025 Apr;44(14):958-967. doi: 10.1038/s41388-024-03267-y. Epub 2025 Jan 10.
2
Alternative splicing of its 5'-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies.其 5'-UTR 的可变剪接限制了 CD20 mRNA 的翻译，并使肿瘤对 CD20 导向的免疫疗法产生耐药性。
Blood. 2023 Nov 16;142(20):1724-1739. doi: 10.1182/blood.2023020400.
3
Targeting alternative splicing in cancer immunotherapy.靶向癌症免疫治疗中的可变剪接
Front Cell Dev Biol. 2023 Aug 10;11:1232146. doi: 10.3389/fcell.2023.1232146. eCollection 2023.
4
CD22 Exon 12 Deletion as an Independent Predictor of Poor Treatment Outcomes in B-ALL.CD22外显子12缺失作为B淋巴细胞白血病治疗效果不佳的独立预测指标
Cancers (Basel). 2023 Mar 4;15(5):1599. doi: 10.3390/cancers15051599.
本文引用的文献
1
Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies.通过广泛的剪接异常调节儿童白血病中的 CD22 蛋白表达：对 CD22 导向免疫治疗的影响。
Blood Cancer Discov. 2022 Mar 1;3(2):103-115. doi: 10.1158/2643-3230.BCD-21-0087.
2
Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma.双等位基因 BCMA 缺失导致多发性骨髓瘤患者对 CAR T 细胞治疗产生耐药。
Nat Commun. 2021 Feb 8;12(1):868. doi: 10.1038/s41467-021-21177-5.
3
CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape.嵌合抗原受体 T 细胞 trogocytosis 和协同杀伤调节肿瘤抗原逃逸。
Nature. 2019 Apr;568(7750):112-116. doi: 10.1038/s41586-019-1054-1. Epub 2019 Mar 27.
4
Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.嵌合抗原受体 19 治疗急性淋巴细胞白血病中靶抗原丢失的遗传机制。
Nat Med. 2018 Oct;24(10):1504-1506. doi: 10.1038/s41591-018-0146-z. Epub 2018 Oct 1.
5
Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell.通过转导单个白血病 B 细胞诱导嵌合抗原受体 T 细胞治疗的耐药性。
Nat Med. 2018 Oct;24(10):1499-1503. doi: 10.1038/s41591-018-0201-9. Epub 2018 Oct 1.
6
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.CD22 靶向 CAR T 细胞可诱导对 CD19 靶向 CAR 免疫疗法初治或耐药的 B-ALL 缓解。
Nat Med. 2018 Jan;24(1):20-28. doi: 10.1038/nm.4441. Epub 2017 Nov 20.
7
Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy.获得CD19阴性髓系表型可使MLL重排的B细胞急性淋巴细胞白血病从CD19嵌合抗原受体T细胞疗法中实现免疫逃逸。
Blood. 2016 May 19;127(20):2406-10. doi: 10.1182/blood-2015-08-665547. Epub 2016 Feb 23.
8
Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy.获得性突变与CD19可变剪接的趋同导致对CART-19免疫疗法产生抗性。
Cancer Discov. 2015 Dec;5(12):1282-95. doi: 10.1158/2159-8290.CD-15-1020. Epub 2015 Oct 29.
9
CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia.CD22 外显子 12 缺失作为人类 B 前体细胞白血病的致病机制。
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16852-7. doi: 10.1073/pnas.1007896107. Epub 2010 Sep 14.
Zotero 插件