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

Immunotherapy. 2019 Dec;11(18):1555-1567. doi: 10.2217/imt-2019-0068. Epub 2019 Dec 9.

Abstract

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.

Keywords: CD31; MMP9; VEGFR2; angiogenesis; anti-CD3 nanobody; pro-angiogenic cytokines.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Angiogenesis Inhibitors / immunology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • CD3 Complex / antagonists & inhibitors*
  • Cytokines / blood
  • Female
  • Immunotherapy
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Single-Domain Antibodies / immunology
  • Single-Domain Antibodies / therapeutic use*
  • Survival Rate
  • Tumor Burden / drug effects

Substances

  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • CD3 Complex
  • Cd3e protein, mouse
  • Cytokines
  • Single-Domain Antibodies