In vivo tumor-suppressing and anti-angiogenic activities of a recombinant anti-CD3ε nanobody in breast cancer mice model

被引:10
作者
Khatibi, Azadeh Sharif [1 ]
Roodbari, Nasim Hayati [1 ]
Majidzade-A, Keivan [2 ]
Yaghmaei, Parichehreh [1 ]
Farahmand, Leila [2 ]
机构
[1] Islamic Azad Univ, Dept Biol, Sci & Res Branch, Tehran, Iran
[2] ACECR, Motamed Canc Inst, Recombinant Prot Dept, Breast Canc Res Ctr, Tehran, Iran
关键词
angiogenesis; anti-CD3; nanobody; CD31; MMP9; pro-angiogenic cytokines; VEGFR2; T-CELL-RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; OKT3; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; IFN-GAMMA; STROMAL FIBROBLASTS; HUMANIZED OKT3; EXPRESSION; REJECTION; ACTIVATION;
D O I
10.2217/imt-2019-0068
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Aim: Achievements in cancer immunotherapy require augmentation of a host's anti-tumor immune response for anti-cancer modality. Materials & methods: Different concentrations of recombinant anti-CD3 nanobody were administered at predetermined time intervals during a 24-day treatment period and then expression of angiogenic biomarkers including VEGFR2, MMP9 and CD31, as well as tumor cell proliferation marker ki67, was determined in tumor sections by immunohistochemistry. Furthermore, expression of cytokines was examined in peripheral blood of mice. Results: Based on our results, administration of nanobody could reduce biomarker expression in tumor sections. Tumor growth was also delayed and survival rate was increased in response to nanobody treatment. Moreover, expression of pro-inflammatory cytokines was reduced. Conclusion: In conclusion, we demonstrated that administration of nanobody could effectively suppress angiogenesis as well as tumor growth.
引用
收藏
页码:1555 / 1567
页数:13
相关论文
共 75 条
  • [1] ALEGRE ML, 1991, J IMMUNOL, V146, P1184
  • [2] Amgen Research Munich GmbH, 2009, [No title captured], Patent No. [US20110275787A1, 20110275787]
  • [3] [Anonymous], 2008, Angiogenesis An Integrative Approach From Science to Medicine
  • [4] Selective Targeting of Interferon γ to Stromal Fibroblasts and Pericytes as a Novel Therapeutic Approach to Inhibit Angiogenesis and Tumor Growth
    Bansal, Ruchi
    Tomar, Tushar
    Ostman, Arne
    Poelstra, Klaas
    Prakash, Jai
    [J]. MOLECULAR CANCER THERAPEUTICS, 2012, 11 (11) : 2419 - 2428
  • [5] IFN-γ can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen
    Beatty, GL
    Paterson, Y
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (10) : 5502 - 5508
  • [6] Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
    Bergers, G
    Brekken, R
    McMahon, G
    Vu, TH
    Itoh, T
    Tamaki, K
    Tanzawa, K
    Thorpe, P
    Itohara, S
    Werb, Z
    Hanahan, D
    [J]. NATURE CELL BIOLOGY, 2000, 2 (10) : 737 - 744
  • [7] Tumor rejection by local interferon gamma induction in established tumors is associated with blood vessel destruction and necrosis
    Briesemeister, Dana
    Sommermeyer, Daniel
    Loddenkemper, Christoph
    Loew, Rainer
    Uckert, Wolfgang
    Blankenstein, Thomas
    Kammertoens, Thomas
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2011, 128 (02) : 371 - 378
  • [8] Modulation of PECAM-1 (CD31] expression in human endothelial cells:: Effect of IFNγ and IL-10
    Buján, J
    Gimeno, MJ
    Prieto, A
    Pascual, G
    Bellón, JM
    Alvarez-Mon, M
    [J]. JOURNAL OF VASCULAR RESEARCH, 1999, 36 (02) : 106 - 113
  • [9] DOES OKT3 MONOCLONAL-ANTIBODY REACT WITH AN ANTIGEN-RECOGNITION STRUCTURE ON HUMAN T-CELLS
    CHANG, TW
    KUNG, PC
    GINGRAS, SP
    GOLDSTEIN, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (03): : 1805 - 1808
  • [10] Bacterial expression systems for recombinant protein production: E. coli and beyond
    Chen, Rachel
    [J]. BIOTECHNOLOGY ADVANCES, 2012, 30 (05) : 1102 - 1107