Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine

Wei, Yuquan; Wang, Qing Ru; Zhao, Xia; Yang, Li; Tian, Li; Lü, You; Kang, Bin; Lu, Changli; Huang, Mei; Lou, Yan Yan; Xiao, Fei; He, Qiu; Shu, Jing; Xie, Xing; Mao, Yun Qiu; Lei, Shong; Luo, Feng; Zhou, Li; Liu, Chong En; Zhou, Hao; Jiang, Yu; Peng, Feng; Yuan, Liang; Qiu, Li; Wu, Yang; Liu, Ji Yan

doi:10.1038/80506

Cited by 218 publications

(213 citation statements)

References 44 publications

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“…After 72 h, the cell number was determined by a trypan blue dye exclusion test, and the percentage inhibition was calculated by the following formula as described: inhibition % = [(NϪN T )/(NϪNo)] × 100, where N is the number of untreated cells cultured for n days, No is the cell number on day 0, and N T is the number of treated cells cultured for n days. 3,36,38 …”

Section: Plasmid Constructionmentioning

confidence: 99%

“…3,18,36 Five mice in each group were anesthetized. Corneal micropockets were created with a cataract knife.…”

Section: Corneal Micropocket Assaymentioning

confidence: 99%

“…43 Immunohistochemistry was done as described. 3,18 Briefly, for CD31 immunostaining, 4% paraformaldehyde-fixed, paraffin-embedded sections from tumor tissues were incubated with a monoclonal rat anti-mouse CD31 at a 1:400 dilution (Pharmingen, San Diego, CA, USA) at 4°C overnight. Following washes in PBS, the secondary antibody, biotinylated rabbit anti-rat antibody at a 1:100 dilution (Dako, Carpinteria, CA, USA) was added.…”

Section: Histological Analysismentioning

confidence: 99%

“…Vessel density was determined by counting the number of microvessels per high-power field in the section with an antibody reactive to CD31, as described. 3,9,26 Immunostaining for PCNA was performed as previously described. 44 Polyclonal rabbit anti-mouse PCNA (Santa Cruz) was used at a dilution of 1:200.…”

Section: Histological Analysismentioning

confidence: 99%

“…1,2 Angiogenesis is important for normal embryonic development and for the development of pathologic conditions such as cancer, rheumatoid arthritis, retinopathies, etc. [3][4][5][6][7][8] Several lines of direct and indirect evidence indicate that the growth and persistence of solid tumors and their metastasis are angiogenesis dependent. 4,[7][8][9][10] As a strategy for cancer therapy, antiangiogenic therapy attempts to stop new vessels from forming around a tumor and break up the existing network of abnormal capillaries that feeds the cancerous mass.…”

Section: Introductionmentioning

confidence: 99%

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A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin

et al. 2002

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Section: Plasmid Constructionmentioning

confidence: 99%

“…3,18,36 Five mice in each group were anesthetized. Corneal micropockets were created with a cataract knife.…”

Section: Corneal Micropocket Assaymentioning

confidence: 99%

Section: Histological Analysismentioning

confidence: 99%

Section: Histological Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin

et al. 2002

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Soluble production and function of vascular endothelial growth factor/basic fibroblast growth factor complex peptide

Zhang

Lao

Huang

et al. 2014

Biotechnology Progress

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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.

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Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen

et al. 2004

Self Cite

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Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibodyproducing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4 + T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.

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Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine

Cited by 218 publications

References 44 publications

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin

Soluble production and function of vascular endothelial growth factor/basic fibroblast growth factor complex peptide

Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen

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