Soluble production and function of vascular endothelial growth factor/basic fibroblast growth factor complex peptide
Authors: Likuan Xiong
Lei Pang
Zhongsong Zhu
Qin Yang
Jiangfang Huang
Yong Tang
Aditi M Sengupta
Jie Deng
Qing Zhang
Ning Deng
Xuejun Lao
Qifang Song
Jianhua Huang
Journal: Biotechnology Progress (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: VEGF; bFGF; fermentation; polypeptide; proangiogenic factor
Affiliations: The State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China., Dept. of Gastrointestinal Surgery; The First Clinical School in Jinan University; Guangzhou China, The Clinical Laboratory of the Third Affiliated Hospital in Sun Yat-Sen University; Guangzhou China, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering; Biomedicine Translational Inst., Jinan University; Guangzhou China, Guangzhou Ming Kang Bioengineering Limited Company; Guangzhou China, Harvard Medical School, Post Graduate Association; Boston MA, USA, Central Laboratory; Baoan Maternal and Child Health Care Hospital; Shenzhen China

Abstract:  Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are important proangiogenic factors in tumor procession. The autocrine and paracrine bFGF and the VEGF in tumor tissue can promote tumor angiogenesis, tumor growth, and metastasis. A VEGF/bFGF Complex Peptide (VBP3) was designed on the basis of epitope peptides from both VEGF and bFGF to elicit in vivo production of anti-bFGF and anti-VEGF antibodies. In this study, we reported on the production of recombinant VBP3 using high cell density fermentation. Fed-batch fermentation for recombinant VBP3 production was conducted, and the production procedure was optimized in a 10-L fermentor. The fraction of soluble VBP3 protein obtained reached 78% of total recombinant protein output under fed-batch fermentation. Purified recombinant VBP3 could inhibit tumor cell proliferation in vitro and stimulate C57BL/6 mice to produce high titer anti-VEGF and anti-bFGF antibodies in vivo. A melanoma-grafted mouse model and an immunohistochemistry assay showed that tumor growth and tumor angiogenesis were significantly inhibited in VBP3-vaccinated mice. These results demonstrated that soluble recombinant VBP3 could be produced by large-scale fermentation, and the product, with good immunogenicity, elicited production of high-titer anti-bFGF and anti-VEGF antibodies, which could be used as a therapeutic tumor vaccine to inhibit tumor angiogenesis and tumor growth. 

Retracted: No

PubPeer comments:
 This paper has a 2016 Erratum to correct affiliations, authors contributions, and funding statements. , 
 Not addressed in the erratum are some unexpected repetitive features in lanes 11 and 12 of Figure 3D. I have marked these with blue and red boxes. Image made darker to bring out more details. ![file] , 
 Correction, March 2022: https: aiche.onlinelibrary.wiley.com doi 10.1002 btpr.3246  *This is a correction for u201cQing Zhang, Xuejun Lao, Jianhua Huang, Zhongsong Zhu, Lei Pang, Yong Tang, Qifang Song, Jiangfang Huang, Jie Deng, Ning Deng, Qin Yang, Aditi M. Sengupta, Likuan Xiong. Soluble production and function of vascular endothelial growth factor basic fibroblast growth factor complex peptide. This erratum corrects Figure 3D, the image of SDS-PAGE analysis of purification of recombinant VBP3, to the image below. The correct figure is presented below. We apologize for this.* ![file] Can the authors please clarify what happened to the original image? How do they explain the repetitive features? , 
 Figure 2 also raises some concerns, as pointed out by a Twitter user. These have not yet been addressed in the two corrections. * Green boxes and arrows: Lanes 12 and 13 look remarkably similar to the mirror image of lanes 14 and 14. ![file] , 
 The same Twitter user, Moritz Ernst Jacob (@Hallfiry ) also noted that Figures 7B and 7C are much more similar than expected, if accounting for a 90 degrees rotation, even if these would represent serial sections. I then noticed that some areas in panel 7C might look repetitive. First, here is the complete figure 7: ![file] Here are panel B and rotated panel C together, with boxes of the same color highlighting areas in panel C that appear to look repetitive, and that also correspond to the position of the brown-stained areas in panel B. The thin black square in panel B denotes the area covered in panel C. ![file] ImageTwin agrees that these look like duplications: ![file] ,