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.
Highlights
Angiogenesis, a critical hallmark of malignancy, is principally driven by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) [1,2,3]
We found that mAb04-MICA maintained the anti-angiogenic and antineoplastic activities of mAb04, and enhanced immunosurveillance activated by the NKG2D pathway
Tumors are characterized by a high proliferation index and require efficient neoangiogenesis, which suggests that targeting VEGF-vascular endothelial growth factor receptor 2 (VEGFR2) signal pathway may be an effective treatment strategy [47, 48]
Summary
Angiogenesis, a critical hallmark of malignancy, is principally driven by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) [1,2,3]. Growth and metastasis have been strongly linked to angiogenesis in the majority of cancers, including metastatic breast carcinoma [4]. Bevacizumab is the first anti-angiogenic agent to be approved by the US FDA targeting VEGF. Available clinical data show that blocking VEGF by Bevacizumab does not completely inhibit tumor angiogenesis [5]. Ramucirumab is a fully human monoclonal (IgG1) anti-VEGFR2 antibody approved for clinical treatment of malignancy by US FDA in 2014. Phase III trials in patients with human epidermal growth factor receptor-2 (HER2−) metastatic breast carcinoma indicated that, overall survival (OS) was not prolonged by the addition of Ramucirumab to the first-line chemotherapeutic drug (Docetaxel)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
