1. Academic Validation
  2. A novel ADC targeting cell surface fibromodulin in a mouse model of triple-negative breast cancer

A novel ADC targeting cell surface fibromodulin in a mouse model of triple-negative breast cancer

  • Breast Cancer. 2022 Aug 18. doi: 10.1007/s12282-022-01393-7.
Mozhan Haji Ghaffari 1 Miganoosh Simonian 2 Ali Salimi 2 Ebrahim Mirzadegan 3 Niloufar Sadeghi 2 Mohammad-Reza Nejadmoghaddam 2 Nasim Ebrahimnezhad 2 Ghazaleh Fazli 2 Ramina Fatemi 2 Ali-Ahmad Bayat 2 Mohammadali Mazloomi 4 Hodjattallah Rabbani 2
Affiliations

Affiliations

  • 1 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
  • 3 Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
  • 4 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
Abstract

Background: Triple-negative breast cancers (TNBCs) are highly aggressive and metastatic. To date, finding efficacious targeted therapy molecules might be the only window of hope to cure Cancer. Fibromodulin (FMOD), is ectopically highly expressed on the surface of Chronic Lymphocytic Leukemia (CLL) and bladder carcinoma cells; thus, it could be a promising molecule for targeted therapy of Cancer. The objective of this study was to evaluate cell surface expression of FMOD in two TNBC cell lines and develop an antibody-drug conjugate (ADC) to target FMOD positive TNBC in vitro and in vivo.

Materials and methods: Two TNBC-derived cell lines 4T1 and MDA-MB-231 were used in this study. The specific binding of anti-FMOD monoclonal antibody (mAb) was evaluated by flow cytometry and its internalization was verified using phAb amine reactive dye. A microtubulin inhibitor Mertansine (DM1) was used for conjugation to anti-FMOD mAb. The binding efficacy of FMOD-ADC was assessed by immunocytochemistry technique. The anti-FMOD mAb and FMOD-ADC Apoptosis induction were measured using Annexin V-FITC and flow cytometry. Tumor growth inhibition of anti-FMOD mAb and FMOD-ADC was evaluated using BALB/c mice injected with 4T1 cells.

Results: Our results indicate that both anti-FMOD mAb and FMOD-ADC recognize cell surface FMOD molecules. FMOD-ADC could induce Apoptosis in 4T1 and MDA-MB-231 cells in vitro. In vivo tumor growth inhibition was observed using FMOD-ADC in 4T1 inoculated BALB/c mice.

Conclusion: Our results suggests high cell surface FMOD expression could be a novel bio-marker TNBCs. Furthermore, FMOD-ADC could be a promising candidate for targeting TNBCs.

Keywords

Apoptosis; Fibromodulin; Flow cytometry; Monoclonal antibody; Triple-negative breast neoplasms.

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