The Design, Characterizations, and Tumor Angiogenesis Inhibition of a Multi-Epitope Peptibody With bFGF/VEGFA
Authors: Simin Zhang
Yong Tang
Ligang Zhang
Wenhui Zhu
Chunyan Liu
Ning Deng
Yanrui Deng
Yinmei Zhang
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Fc domain; VEGFA; bFGF; peptibody; tumor angiogenesis.
Affiliations: Department of Biology, Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Jinan University, Guangzhou, China.

Abstract:  Tumor angiogenesis is dependent on growth factors, and inhibition of their pathways is one of the promising strategies in cancer therapy. However, resistance to single pathway has been a great concern in clinical trials so that it necessitates multiple targetable factors for developing tumor angiogenesis inhibitors. Moreover, the strategy of Fc fusion protein is an attractive platform for novel peptide agents, which gains increasing importance with FDA approval because of better immunogenicity and stability. Here, we applied the Fc fusion protein concept to bFGF/VEGFA pathways and designed a multi-epitope Peptibody with immunogenic peptides derived from human bFGF and VEGFA sequences. Immunization with Peptibody could elicit high-titer anti-bFGF and anti-VEGFA antibodies, activate T cells, and induce Th1/Th2-type cytokines. In in vitro experiments, the isolated anti-Peptibody antibody inhibited the proliferation and migration of A549 cells and human umbilical vein endothelial cells (HUVECs) by decreasing the MAPK/Akt/mTOR signal pathways. In the murine tumor model, pre-immunization with Peptibody suppressed the tumor growth and neovascularization of lung cancer by decreasing the production of bFGF/VEGFA/PDGF, the MAPK/Akt/mTOR signal pathways, and the activation of suppressive cells in tumor sites. Further, the biological characterizations of the recombinant Peptibody were investigated systematically, including protein primary structure, secondary structure, stability, and toxicity. Collectively, the results highlighted the strategy of bFGF/VEGFA pathways and Fc fusion protein in suppressing tumor progression and angiogenesis, which emphasized the potential of multiple targetable factors for producing enduring clinical responses in tumor patients. 

Retracted: Yes

PubPeer comments:
 January 2021 retraction. The retraction notice is found here: https: www.frontiersin.org articles 10.3389 fonc.2020.644690 fullhttps: www.frontiersin.org articles 10.3389 fonc.2020.644690 full It reads:  *Following publication, concerns were raised regarding the integrity of Figures 3B and 3D. An investigation was conducted in accordance with Frontiers guidelines and the authors failed to provide a satisfactory explanation.* *This retraction was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers.* , 
 A post-mortem analysis of Figure 3B. * Several cuts appear to be visible. ![file] A post-mortem analysis of Figure 3D. * Green and yellow boxes: two sets of c) and d) panels appear to overlap with each other. ![file] , 
 In Figure 3B, to make the results more convincing and avoid confusion, we have revised the results of Western blotting with some new blots. We should provide replicate blots of raw data to show that anti-Peptibody antibody could significantly down-regulate the levels of mTOR, p-Akt and p-MAPK. The new results has been assembled into the new Figure 3 and the replicate raw data has been attached separately. In Figure 3D, due to our negligence, we used the migrated images of group (c) to assemble group (d) in mistake and we did not check out this accident at the beginning of our submission. We have used the right migrated images of group (d) to re-assemble this part and the raw images of group (d) have been attached. ![file] , 
 In Figure 3B, to make the results more convincing and avoid confusion, we have revised the results of Western blotting with some new blots. We should provide replicate blots of raw data to show that anti-Peptibody antibody could significantly down-regulate the levels of mTOR, p-Akt and p-MAPK. The new results has been assembled into the new Figure 3 and the replicate raw data has been attached separately. In Figure 3D, due to our negligence, we used the migrated images of group (c) to assemble group (d) in mistake and we did not check out this accident at the beginning of our submission. We have used the right migrated images of group (d) to re-assemble this part and the raw images of group (d) have been attached. , 
 Results are either convincing and then you can publish them, or they are not and then you do not publish them.... making results more convincing is just another expression for  manipulating data . Therefore the retraction seems absolutely fair. By the way - when looking at your  corrected figure: the upper Western Blot for mTOR in (b) still seems to contain cut copy pasted bands. , 
 --Retracted-- https: www.frontiersin.org articles 10.3389 fonc.2020.644690 full A Retraction of the Original Research article The Design, Characterizations, and Tumor Angiogenesis Inhibition of a Multi-Epitope Peptibody With bFGF VEGFA by Zhang L, Deng Y, Zhang Y, Liu C, Zhang S, Zhu W, Tang Y and Deng N (2020). Front. Oncol. 10:1190. doi: 10.3389 fonc.2020.01190 Following publication, concerns were raised regarding the integrity of Figures 3B and 3D. An investigation was conducted in accordance with Frontiers guidelines and the authors failed to provide a satisfactory explanation. This retraction was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers. , 
 Dear Heterochasta Lasioplaca, we are very appreciated for you and your colleagues to point out the misused data in our manuscript. Before your early email, we had been informed of the mistakes from the editorial department of Frontiers in Oncology. We actively contacted the editorial department and tried to make some revision for the misused data. The revised figure had been uploaded in the PubPeer record above. We deeply realized the faults so we had applied for the retraction of this article to the editorial department. We have read the retraction which was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers. All the authors agree to this retraction. We are very sorry for the mistakes and inconvenience we made. We will completely revise the data according to the journal guidelines before next submission. We guarantee that these mistakes will not happen again and we desire your forgiveness in a sincere manner. ,