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抗体药物偶联物（A1mcMMAF）联合卡铂治疗针对癌胚糖蛋白 5T4 的靶向治疗改善卵巢癌异种移植模型的生存。

Combination Treatment with an Antibody-Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer.

机构信息

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 5th Floor Research, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK.

Oncology Research and Development, Pfizer Inc., 401 N. Middletown Road, Pearl River, NY, 10954, USA.

出版信息

Target Oncol. 2019 Aug;14(4):465-477. doi: 10.1007/s11523-019-00650-8.

DOI:10.1007/s11523-019-00650-8
PMID:31332693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6684567/
Abstract

BACKGROUND

Recurrence occurs in over 75% of women with epithelial ovarian cancer despite optimal treatment. Selectively killing tumour cells thought to initiate relapse using an antibody-drug conjugate could prolong progression-free survival and offer an improved side-effect profile. A1mcMMAF is an antibody-drug conjugate designed to target cells expressing the tumour-associated antigen 5T4. It has shown to be efficacious in various cell line models and have a greater impact when combined with routine chemotherapeutic regimes.

OBJECTIVES

This study aims to explore the potential for the use of a 5T4 antibody-drug conjugate in women with ovarian cancer both as a monotherapy and in combination with platinum-based chemotherapy.

METHODS

Immunohistochemical analysis was used to assess 5T4 expression in tumours from patients with ovarian cancer. Effectiveness of A1mcMMAF therapy as a single agent and in combination with carboplatin was assessed in vitro in the ovarian cancer cell line SKOV3 and confirmed in vivo using a serial bioluminescence assay in a SKOV3 xenograft model of ovarian cancer.

RESULTS

5T4 is confirmed as suitably expressed in epithelial ovarian cancers prior to adjuvant therapy and is an independent predictor of poor survival. A1mcMMAF showed specific activity, both in vitro and in vivo, against SKOV3 ovarian cancer cells. When used in combination with carboplatin, in vivo tumour growth was inhibited resulting in prolonged survival in a SKOV3 xenograft model.

CONCLUSIONS

These data support further investigation of A1mcMMAF in combination with platinum-based chemotherapy in ovarian and other cancer treatments.

摘要

背景

尽管进行了最佳治疗，上皮性卵巢癌患者中有超过 75%的患者仍会复发。使用抗体药物偶联物选择性杀伤被认为引发复发的肿瘤细胞，可以延长无进展生存期，并提供改善的副作用谱。A1mcMMAF 是一种旨在靶向表达肿瘤相关抗原 5T4 的细胞的抗体药物偶联物。它已在各种细胞系模型中显示出疗效，并且与常规化疗方案联合使用时效果更大。

目的

本研究旨在探索 5T4 抗体药物偶联物在卵巢癌患者中的应用潜力，无论是作为单一药物还是与铂类化疗联合使用。

方法

免疫组织化学分析用于评估卵巢癌患者肿瘤中的 5T4 表达。在卵巢癌细胞系 SKOV3 中评估 A1mcMMAF 作为单一药物和与卡铂联合治疗的有效性，并在 SKOV3 卵巢癌异种移植模型中使用连续生物发光测定法进行体内验证。

结果

5T4 在辅助治疗前被证实在上皮性卵巢癌中表达适当，是不良生存的独立预测因子。A1mcMMAF 在体外和体内对 SKOV3 卵巢癌细胞均表现出特异性活性。当与卡铂联合使用时，体内肿瘤生长受到抑制，导致 SKOV3 异种移植模型中的存活时间延长。

结论

这些数据支持进一步研究 A1mcMMAF 与铂类化疗联合用于卵巢癌和其他癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/43465fb5480d/11523_2019_650_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/11c48e0e9ad6/11523_2019_650_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/46b23b23ffd7/11523_2019_650_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/43465fb5480d/11523_2019_650_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/11c48e0e9ad6/11523_2019_650_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/46b23b23ffd7/11523_2019_650_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b317/6684567/43465fb5480d/11523_2019_650_Fig5_HTML.jpg

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1
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2
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Medicines (Basel). 2018 Feb 1;5(1):16. doi: 10.3390/medicines5010016.
3
Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer.卵巢癌中新型聚ADP核糖聚合酶抑制剂联合策略
在肌肉浸润性膀胱癌患者来源的异种移植模型中，T-DM1与铂类化疗的联合应用。
Iran J Basic Med Sci. 2022 Jul;25(7):816-821. doi: 10.22038/IJBMS.2022.63509.14005.
4
Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.嵌合抗原受体设计及其在卵巢癌治疗中的疗效。
Int J Mol Sci. 2021 Mar 28;22(7):3495. doi: 10.3390/ijms22073495.
Curr Opin Obstet Gynecol. 2018 Feb;30(1):7-16. doi: 10.1097/GCO.0000000000000428.
4
Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer.卵巢癌中针对肿瘤抗原 5T4 的嵌合抗原受体 T 细胞疗法的临床前评估。
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5
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6
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