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Table 1 Protein/peptide vaccines against tumor angiogenesis-associated antigens evaluated for safety in human and experimental studies

From: Safety of targeting tumor endothelial cell antigens

Vaccine Tumor type Adverse events/potential autoimmunity References
Fibroblast growth factor (FGF)-2 peptide Murine pulmonary metastatic cancer No effect on wound healing, reproduction, organogenesis in offspring [61]
Vascular endothelial growth factor receptor (VEGFR)-2 FLK1 DNA Murine melanoma, colon carcinoma and lung carcinoma, metastatic pulmonary metastasis No impairment of fertility, neuromuscular performance or hematopoiesis, slight delay in wound healing [62]
VEGFR2 polypeptides, Listeria monocytogenes vector, microbial adjuvant, listeriolysin-O Murine HER2 + breast cancer No effect on wound healing or fertility [63]
VEGF and Neisseria meningitidis outer membrane Numerous in rats, rabbits, primates No effect on skin deep wound healing [64]
Endoglin DNA, Salmonella typhimurium vector Murine tumors No effect on wound healing [65]
Survivin DNA Listeria monocytogenes vector Murine pulmonary metastases of non-small cell lung carcinoma No effect on wound healing or fertility [66]
Tumor endothelial marker (TEM)-1 DNA fused to domain of the C fragment of tetanus toxoid Numerous murine models No effect on wound healing or reproduction [67]
Notch ligand delta-like ligand 4 (DLL4) DNA Murine mammary carcinoma No effect on wound healing [68]
CIGB-247, VEGF variant with bacterial adjuvant Phase I clinical study of patients with advanced solid tumors Only grade 1–2 adverse events [50]
VEGFR2 peptide (VEGFR2-169) plus gemcitabine Phase I clinical study of advanced pancreatic cancer No severe adverse events, 83 % had immunological reaction at injection site [51]
CIMAvax® epidermal growth factor (EGF) Human clinical study of patients undergoing surgery during treatment with CIMAvax® EGF No wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or bleeding associated with surgery during treatment with CIMAvax® EGF occurred [69]