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

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]