Mimotope vaccination for epitope-specific induction of anti-VEGF antibodies.
BACKGROUND
Tumor angiogenesis is critical for tumor growth, infiltration and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and targeting it is important in reducing angiogenesis. Bevacizumab (Avastin), a monoclonal antibody that reacts directly against VEGF, has been demonstrated to be an effective treatment for various cancers such as rectal cancer, colon carcinoma, and non-small cell lung cancer, etc.


RESULTS
In the current study, we used the phage display technique to generate mimotopes that complemented the screening Avastin antibody (Ab). The candidate mimotopes of VEGF were isolated from a 12-mer peptide library. The phage displaying peptide DHTLYTPYHTHP (designated as 12P) exhibited high affinity to Avastin. The chemically synthesized 12P was conjugated to keyhole limpet hemocyanin (KLH) by glutaraldehyde (GA) to form vaccine KLH-12 peptide (KLH-12P). This epitope vaccine significantly induced humoral immunity in mice. The blood serum from KLH-12P-immunized mice associated with VEGF and blocked its binding to VEGFR, thus inhibiting vascular endothelial cell proliferation and migration.


CONCLUSIONS
Our data indicate that the isolated mimotope 12P reported here could potentially elicit specific antibodies against VEGF and result in the induction of anti-angiogenesis responses.
The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China. Zhangw90@fmmu.edu.cn.
Weina
W
Li
Yonggang
Y
Ran
Meng
M
Li
Kuo
K
Zhang
Xin
X
Qin
Xiaochang
X
Xue
Cun
C
Zhang
Qiang
Q
Hao
Wei
W
Zhang
Yingqi
Y
Zhang
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005976:Glutaral / Q000494:pharmacology; D006433:Hemocyanins / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000517:prevention & control; D019151:Peptide Library; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014611:Vaccination / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology
D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D019151:Peptide Library; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D005976:Glutaral