Cancer anti-angiogenesis vaccines: Is the tumor vasculature antigenically unique?

Journal of Translational Medicine

Volumn 13, Issue 1, 2015, Pages

  Wagner, Samuel C ^a   Ichim, Thomas E ^a   Ma, Hong ^a   Szymanski, Julia ^a   Perez, Jesus A ^b   Lopez, Javier ^b   Bogin, Vladimir ^a   Patel, Amit N ^c   Marincola, Francisco M ^d   Kesari, Santosh ^e  

^a Batu Biologics   (United States)

^b Pan Am Cancer Treatment Center   (Mexico)

^c UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^d SIDRA MEDICAL AND RESEARCH CENTER   (Qatar)

^e UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; ANGIOMOTIN DNA VACCINE; ANGIOPOIETIN RECEPTOR VACCINE; BASIC FIBROBLAST GROWTH FACTOR PEPTIDE VACCINE; CANCER VACCINE; CIGB 247; CIMAVAX; DNA VACCINE; ENDOGLIN DNA VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR; ETARACIZUMAB; FIBROBLAST GROWTH FACTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 1; GEMCITABINE; HP59 PEPTIDE VACCINE; PEPTIDE VACCINE; ROBO4 IMMUNOGLOBULIN FC FRAGMENT FUSION PEPTIDE VACCINE; SURVIVIN VACCINE; TEM8 DNA VACCINE; TUMOR ENDOTHELIAL MARKER 1 PEPTIDE VACCINE; UNCLASSIFIED DRUG; VALLOVAX; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 2 169 PEPTIDE VACCINE; VITRONECTIN RECEPTOR;

ANTIANGIOGENIC ACTIVITY; ANTIBODY RESPONSE; ANTINEOPLASTIC ACTIVITY; AUTOIMMUNITY; BREAST CANCER; CANCER CLASSIFICATION; CANCER IMMUNIZATION; CANCER SURVIVAL; CELLULAR IMMUNITY; COLON CANCER; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; ENDOTHELIUM CELL; HUMAN; HUMORAL IMMUNITY; LEWIS CARCINOMA; LIVER CELL CARCINOMA; LUNG CARCINOMA; LUNG METASTASIS; MELANOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PROTEIN ANALYSIS; PROTEIN EXPRESSION; REVIEW; SOLID TUMOR; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION; UMBILICAL VEIN ENDOTHELIAL CELL; UNSPECIFIED SIDE EFFECT; IMMUNOLOGY; NEOPLASM; NEOVASCULARIZATION, PATHOLOGIC; VASCULARIZATION;

CANCER VACCINES; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 84945931147     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/s12967-015-0688-5     Document Type: Review

References (122)

1. Stockmann C, et al. The impact of the immune system on tumor: angiogenesis and vascular remodeling. Front Oncol. 2014;4:69.
2. Hirst DG, Denekamp J, Hobson B. Proliferation kinetics of endothelial and tumour cells in three mouse mammary carcinomas. Cell Tissue Kinet. 1982;15(3):251-61.
3. Denekamp J, Hobson B. Endothelial-cell proliferation in experimental tumours. Br J Cancer. 1982;46(5):711-20.
4. Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer. 1984;49(4):405-13.
5. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182-6.
6. Folkman J. Fighting cancer by attacking its blood supply. Sci Am. 1996;275(3):150-4.
7. Ellis LM, Fidler IJ. Finding the tumor copycat. Therapy fails, patients don't. Nat Med. 2010;16(9):974-5.
8. Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med. 2012;2(3):a006536.
9. Cines DB, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91(10):3527-61.
10. Nagy JA, Dvorak AM, Dvorak HF. VEGF-A and the induction of pathological angiogenesis. Annu Rev Pathol. 2007;2:251-75.
11. Jain RK. Determinants of tumor blood flow: a review. Cancer Res. 1988;48(10):2641-58.
12. Less JR, et al. Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions. Cancer Res. 1991;51(1):265-73.
13. Goel S, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011;91(3):1071-121.
14. Bussolati B, et al. Altered angiogenesis and survival in human tumor-derived endothelial cells. FASEB J. 2003;17(9):1159-61.
15. Grange C, et al. Isolation and characterization of human breast tumor-derived endothelial cells. Oncol Rep. 2006;15(2):381-6.
16. Xiong YQ, et al. Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells. Clin Cancer Res. 2009;15(15):4838-46.
17. Hida K, Klagsbrun M. A new perspective on tumor endothelial cells: unexpected chromosome and centrosome abnormalities. Cancer Res. 2005;65(7):2507-10.
18. Taylor SM, et al. Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood. 2010;116(16):3108-17.
19. Akiyama K, et al. Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol. 2012;180(3):1283-93.
20. Griffioen AW. Anti-angiogenesis: making the tumor vulnerable to the immune system. Cancer Immunol Immunother. 2008;57(10):1553-8.
21. Griffioen AW, et al. Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. Blood. 1996;88(2):667-73.
22. Griffioen AW, et al. Angiogenesis inhibitors overcome tumor induced endothelial cell anergy. Int J Cancer. 1999;80(2):315-9.
23. Dirkx AE, et al. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J. 2006;20(6):621-30.
24. Motz GT, et al. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med. 2014;20(6):607-15.
25. Seaman S, et al. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell. 2007;11(6):539-54.
26. Wei YQ, et al. Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen. Proc Natl Acad Sci USA. 2001;98(20):11545-50.
27. Gavilondo JV, et al. Specific active immunotherapy with a VEGF vaccine in patients with advanced solid tumors. Results of the CENTAURO antigen dose escalation phase I clinical trial. Vaccine. 2014;32(19):2241-50.
28. Katoh O, et al. Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation. Cancer Res. 1995;55(23):5687-92.
29. Hattori K, et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med. 2001;193(9):1005-14.
30. Larrivee B, et al. Vascular endothelial growth factor receptor-2 induces survival of hematopoietic progenitor cells. J Biol Chem. 2003;278(24):22006-13.
31. Chen R, et al. Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide. Oncol Rep. 2015;33(5):2269-76.
32. McKinney KA, et al. Effect of a novel DNA vaccine on angiogenesis and tumor growth in vivo. Arch Otolaryngol Head Neck Surg. 2010;136(9):859-64.
33. Liang PH, et al. Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth. Cancer Immunol Immunother. 2010;59(1):93-101.
34. Xie K, et al. Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models. Genet Vaccines Ther. 2009;7:10.
35. Liu JY, et al. Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2. Blood. 2003;102(5):1815-23.
36. Zuo SG, et al. Orally administered DNA vaccine delivery by attenuated Salmonella typhimurium targeting fetal liver kinase 1 inhibits murine Lewis lung carcinoma growth and metastasis. Biol Pharm Bull. 2010;33(2):174-82.
37. Wada S, et al. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005;65(11):4939-46.
38. Ishizaki H, et al. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006;12(19):5841-9.
39. Niethammer AG, et al. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med. 2002;8(12):1369-75.
40. Li Y, et al. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med. 2002;195(12):1575-84.
41. Seavey MM, et al. An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu+ breast tumors in a mouse model. J Immunol. 2009;182(9):5537-46.
42. Miyazawa M, et al. Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci. 2010;101(2):433-9.
43. Okamoto I, et al. Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Cancer Sci. 2012;103(12):2135-8.
44. Hayashi H, et al. Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor. Cancer Sci. 2013;104(1):98-104.
45. Suzuki H, et al. Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer. J Transl Med. 2013;11:97.
46. Magnusson PU, et al. Fibroblast growth factor receptor-1 expression is required for hematopoietic but not endothelial cell development. Arterioscler Thromb Vasc Biol. 2005;25(5):944-9.
47. Burger PE, et al. Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells. Blood. 2002;100(10):3527-35.
48. He QM, et al. Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice. J Biol Chem. 2003;278(24):21831-6.
49. Zheng SJ, et al. Synergistic anti-tumor effect of recombinant chicken fibroblast growth factor receptor-1-mediated anti-angiogenesis and low-dose gemcitabine in a mouse colon adenocarcinoma model. World J Gastroenterol. 2007;13(17):2484-9.
50. Li M, et al. bFGF peptide combined with the pVAX-8CpG plasmid as adjuvant is a novel anticancer vaccine inducing effective immune responses against Lewis lung carcinoma. Mol Med Rep. 2012;5(3):625-30.
51. Plum SM, et al. Administration of a liposomal FGF-2 peptide vaccine leads to abrogation of FGF-2-mediated angiogenesis and tumor development. Vaccine. 2000;19(9-10):1294-303.
52. Plum SM, et al. Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction. Immunopharmacol Immunotoxicol. 2004;26(1):29-41.
53. Liu Z, Wang F, Chen X. Integrin alpha(v)beta(3)-Targeted Cancer Therapy. Drug Dev Res. 2008;69(6):329-39.
54. Wilder RL. Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis. 2002; 61(Suppl 2):ii96-ii99.
55. McNeel DG, et al. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. Clin Cancer Res. 2005;11(21):7851-60.
56. Bratt A, et al. Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains. Gene. 2002;298(1):69-77.
57. Holmgren L, et al. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc Natl Acad Sci USA. 2006;103(24):9208-13.
58. Arigoni M, et al. A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors. Angiogenesis. 2012;15(2):305-16.
59. Duff SE, et al. CD105 is important for angiogenesis: evidence and potential applications. FASEB J. 2003;17(9):984-92.
60. Basilio-de-Oliveira RP, Nunes VL. Pannain, Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors. World J Gastroenterol. 2015;21(22):6924-30.
61. Svatek RS, et al. Preoperative plasma endoglin levels predict biochemical progression after radical prostatectomy. Clin Cancer Res. 2008;14(11):3362-6.
62. Huang FY, et al. Bacterial surface display of endoglin by antigen 43 induces antitumor effectiveness via bypassing immunotolerance and inhibition of angiogenesis. Int J Cancer. 2014;134(8):1981-90.
63. Jarosz M, et al. Therapeutic antitumor potential of endoglin-based DNA vaccine combined with immunomodulatory agents. Gene Ther. 2013;20(3):262-73.
64. Ryan BM, O'Donovan N, Duffy MJ. Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009;35(7):553-62.
65. Lladser A, et al. Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma. Cancer Immunol Immunother. 2010;59(1):81-92.
66. Lladser A, et al. Naked DNA immunization as an approach to target the generic tumor antigen survivin induces humoral and cellular immune responses in mice. Immunobiology. 2006;211(1-2):11-27.
67. Park KW, et al. Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev Biol. 2003;261(1):251-67.
68. Bedell VM, et al. Roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci U S A. 2005;102(18):6373-8.
69. Jones CA, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat Med. 2008;14(4):448-53.
70. Seth P, et al. Magic roundabout, a tumor endothelial marker: expression and signaling. Biochem Biophys Res Commun. 2005;332(2):533-41.
71. Cai H, et al. Roundabout 4 regulates blood-tumor barrier permeability through the modulation of ZO-1, Occludin, and Claudin-5 expression. J Neuropathol Exp Neurol. 2015;74(1):25-37.
72. Zhuang X, et al. Robo4 vaccines induce antibodies that retard tumor growth. Angiogenesis. 2015;18(1):83-95.
73. Acevedo LM, Weis SM, Cheresh DA. Robo4 counteracts VEGF signaling. Nat Med. 2008;14(4):372-3.
74. Lou YY, et al. Immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken homologous integrin beta3. Immunol Invest. 2002;31(1):51-69.
75. Daly C, et al. Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition. Cancer Res. 2013;73(1):108-18.
76. Niu G, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 2002;21(13):2000-8.
77. Arteaga CL. The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J Clin Oncol. 2001;19(18 Suppl):32S-40S.
78. Fontanini G, et al. Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival. Clin Cancer Res. 1998;4(1):241-9.
79. Grandis JR, et al. Normalization of EGFR mRNA levels following restoration of wild-type p53 in a head and neck squamous cell carcinoma cell line. Int J Oncol. 1998;13(2):375-8.
80. Garcia B, et al. Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine. Clin Cancer Res. 2008;14(3):840-6.
81. Fernandez Lorente A, et al. Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax(R) EGF. World J Surg Oncol. 2013;11:275.
82. Fu C, et al. Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis. Clin Cancer Res. 2001;7(12):4182-94.
83. Xue Y, et al. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nat Med. 2012;18(1):100-10.
84. Pietras K, et al. Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med. 2008;5(1):e19.
85. Falcon BL, et al. Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-B. Am J Pathol. 2011;178(6):2920-30.
86. Hosaka K, et al. Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis. Nat Commun. 2013;4:2129.
87. Kaplan CD, et al. A novel DNA vaccine encoding PDGFRbeta suppresses growth and dissemination of murine colon, lung and breast carcinoma. Vaccine. 2006;24(47-48):6994-7002.
88. Brady J, et al. Human endosialin (tumor endothelial marker 1) is abundantly expressed in highly malignant and invasive brain tumors. J Neuropathol Exp Neurol. 2004;63(12):1274-83.
89. Rouleau C, et al. Endosialin protein expression and therapeutic target potential in human solid tumors: sarcoma versus carcinoma. Clin Cancer Res. 2008;14(22):7223-36.
90. Carson-Walter EB, et al. Characterization of TEM1/endosialin in human and murine brain tumors. BMC Cancer. 2009;9:417.
91. Bagley RG. Endosialin: from vascular target to biomarker for human sarcomas. Biomark Med. 2009;3(5):589-604.
92. MacFadyen JR, et al. Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium. FEBS Lett. 2005;579(12):2569-75.
93. Christian S, et al. Endosialin (Tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. Am J Pathol. 2008;172(2):486-94.
94. Facciponte JG, et al. Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature. J Clin Invest. 2014;124(4):1497-511.
95. St. Croix B, et al. Genes expressed in human tumor endothelium. Science. 2000;289(5482):1197-202.
96. Felicetti P, et al. Tumor endothelial marker 8 enhances tumor immunity in conjunction with immnization against differentiation Ag. Cytotherapy. 2007;9(1):23-34.
97. Ruan Z, et al. DNA vaccine against tumor endothelial marker 8 inhibits tumor angiogenesis and growth. J Immunother. 2009;32(5):486-91.
98. Yang X, Zhu H, Hu Z. Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth. Vaccine. 2010;28(43):7130-5.
99. Liu P, et al. Anti-tumor angiogenesis effect of genetic fusion vaccine encoding murine beta-defensin 2 and tumor endothelial marker-8 in a CT-26 murine colorectal carcinoma model. Int J Clin Exp Med. 2015;8(3):4744-52.
100. Wei YQ, et al. Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine. Nat Med. 2000;6(10):1160-6.
101. Okaji Y, et al. Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity. Cancer Sci. 2004;95(1):85-90.
102. Yoshiura K, et al. Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line. J Exp Clin Cancer Res. 2009;28:13.
103. Scappaticci FA, Nolan GP. Induction of anti-tumor immunity in mice using a syngeneic endothelial cell vaccine. Anticancer Res. 2003;23(2B):1165-72.
104. Corsini E, et al. Immunotherapy with bovine aortic endothelial cells in subcutaneous and intracerebral glioma models in rats: effects on survival time, tumor growth, and tumor neovascularization. Cancer Immunol Immunother. 2004;53(11):955-62.
105. Zhang W, Liu JN, Tan XY. Vaccination with xenogeneic tumor endothelial proteins isolated in situ inhibits tumor angiogenesis and spontaneous metastasis. Int J Cancer. 2009;125(1):124-32.
106. Okaji Y, et al. Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy. Eur J Cancer. 2008;44(3):383-90.
107. Tanaka M, et al. Human umbilical vein endothelial cell vaccine therapy in patients with recurrent glioblastoma. Cancer Sci. 2013;104(2):200-5.
108. Friedman HS, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733-40.
109. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod. 2001;64(4):1033-40.
110. Harandi A. Immunoplacental therapy, a potential multi-epitope cancer vaccine. Med Hypotheses. 2006;66(6):1182-7.
111. Holtan SG, et al. Cancer and pregnancy: parallels in growth, invasion, and immune modulation and implications for cancer therapeutic agents. Mayo Clin Proc. 2009;84(11):985-1000.
112. Vonnahme KA, et al. Placental vascularity and growth factor expression in singleton, twin, and triplet pregnancies in the sheep. Endocrine. 2008;33(1):53-61.
113. Muschol-Steinmetz C, et al. Function of survivin in trophoblastic cells of the placenta. PLoS One. 2013;8(9):e73337.
114. Olsen DT, et al. Purification and characterization of a soluble calnexin from human placenta. Protein Expr Purif. 2013;92(1):105-11.
115. Troyanovsky B, et al. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol. 2001;152(6):1247-54.
116. Liao WX, et al. Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia. Biol Reprod. 2012;86(4):111.
117. Holmgren L, et al. Angiogenesis during human extraembryonic development involves the spatiotemporal control of PDGF ligand and receptor gene expression. Development. 1991;113(3):749-54.
118. Moscatelli DA, et al. Purification and biological activities of an angiogenesis factor from human placenta. Anticancer Res. 1986;6(4):861-3.
119. Ugele B, Lange F. Isolation of endothelial cells from human placental microvessels: effect of different proteolytic enzymes on releasing endothelial cells from villous tissue. Vitro Cell Dev Biol Anim. 2001;37(7):408-13.
120. Kacemi A, et al. Isolation of villous microvessels from the human placenta. C R Acad Sci III. 1997;320(2):171-7.
121. Schugar RC, et al. High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal stromal cells from whole primitive human umbilical cord tissue. J Biomed Biotechnol. 2009;2009:789526.
122. Ichim TE, et al. Induction of tumor inhibitory anti-angiogenic response through immunization with interferon Gamma primed placental endothelial cells: ValloVax. J Transl Med. 2015;13:90.