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与MICA融合的VEGFR2靶向抗体可刺激NKG2D介导的免疫监视，并对乳腺癌表现出强大的抗肿瘤活性。

VEGFR2 targeted antibody fused with MICA stimulates NKG2D mediated immunosurveillance and exhibits potent anti-tumor activity against breast cancer.

作者信息

Xie Wei, Liu Fang, Wang Youfu, Ren Xueyan, Wang Tong, Chen Zhiguo, Tang Mingying, Sun Fumou, Li Zhaoting, Wang Min, Zhang Juan

机构信息

State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.

出版信息

Oncotarget. 2016 Mar 29;7(13):16445-61. doi: 10.18632/oncotarget.7501.

DOI:10.18632/oncotarget.7501
PMID:26909862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4941327/
Abstract

Binding of MHC class I-related chain molecules A and B (MICA/B) to the natural killer (NK) cell receptor NK group 2, member D (NKG2D) is thought critical for activating NK-mediated immunosurveillance. Angiogenesis is important for tumor growth and interfering with angiogenesis using the fully human IgG1 anti-VEGFR2 (vascular endothelial growth factor receptor 2) antibody (mAb04) can be effective in treating malignancy. In an effort to make mAb04 more effective we have generated a novel antibody fusion protein (mAb04-MICA) consisting of mAb04 and MICA. We found that mAb04-MICA maintained the anti-angiogenic and antineoplastic activities of mAb04, and also enhanced immunosurveillance activated by the NKG2D pathway. Moreover, in human breast tumor-bearing nude mice, mAb04-MICA demonstrated superior anti-tumor efficacy compared to combination therapy of mAb04 + Docetaxel or Avastin + Docetaxel, highlighting the immunostimulatory effect of MICA. In conclusion, mAb04-MICA provided new inspiration for anti-tumor treatment and had prospects for clinical application.

摘要

MHC I类相关链分子A和B（MICA/B）与自然杀伤（NK）细胞受体NK2组D成员（NKG2D）的结合被认为对激活NK介导的免疫监视至关重要。血管生成对肿瘤生长很重要，使用全人源IgG1抗血管内皮生长因子受体2（VEGFR2）抗体（mAb04）干扰血管生成可有效治疗恶性肿瘤。为了使mAb04更有效，我们制备了一种由mAb04和MICA组成的新型抗体融合蛋白（mAb04-MICA）。我们发现mAb04-MICA保留了mAb04的抗血管生成和抗肿瘤活性，还增强了由NKG2D途径激活的免疫监视。此外，在荷人乳腺肿瘤的裸鼠中，mAb04-MICA与mAb04+多西他赛或阿瓦斯汀+多西他赛联合治疗相比，显示出更好的抗肿瘤疗效，突出了MICA的免疫刺激作用。总之，mAb04-MICA为抗肿瘤治疗提供了新的思路，具有临床应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/e219623482d3/oncotarget-07-16445-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/e219623482d3/oncotarget-07-16445-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/f369a9c4d2fd/oncotarget-07-16445-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/eb21635a3a7a/oncotarget-07-16445-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/83f34d19804e/oncotarget-07-16445-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/0ed1443c7063/oncotarget-07-16445-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad6/4941327/80cb677e4fda/oncotarget-07-16445-g009.jpg
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