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Updated: Jan 21, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
A Bispecific Antibody-Based Approach for Targeting Mesothelin in Triple Negative Breast Cancer
Joanie Del Bano1, Rémy Florès-Florès2, Emmanuelle Josselin1
1Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, France.
Abstract:
Triple negative breast cancers (TNBC) remain a major medical challenge due to poor prognosis and limited treatment options. Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane protein with restricted normal expression and high level expression in a large proportion of TNBC, thus qualifying as an attractive target. Its overexpression in breast tumors has been recently correlated with a decreased disease-free survival and an increase of distant metastases. The objective of the study was to investigate the relevance of a bispecific antibody-based immunotherapy approach through mesothelin targeting and CD16 engagement using a Fab-like bispecific format (MesobsFab). Using two TNBC cell lines with different level of surface mesothelin and epithelial/mesenchymal phenotypes, we showed that, in vitro, MesobsFab promotes the recruitment and penetration of NK cells into tumor spheroids, induces potent dose-dependent cell-mediated cytotoxicity of mesothelin-positive tumor cells, cytokine secretion, and decreases cell invasiveness. MesobsFab was able to induce cytotoxicity in resting human peripheral blood mononuclear cells (PBMC), mainly through its NK cells-mediated antibody dependent cell cytotoxicity (ADCC) activity. In vivo, the anti-tumor effect of MesobsFab depends upon a threshold of MSLN density on target cells. Collectively our data support mesothelin as a relevant therapeutic target for the subset of TNBC that overexpresses mesothelin characterized by a low overall and disease-free survival as well as the potential of MesobsFab as antibody-based immunotherapeutics.
Insights
This study explores MesobsFab, a bispecific antibody immunotherapy targeting mesothelin (MSLN) in triple-negative breast cancer (TNBC). MesobsFab effectively eliminates MSLN-positive TNBC cells by engaging natural killer (NK) cells, offering a promising new treatment avenue.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to poor prognosis and limited treatment options.
- Mesothelin (MSLN) is overexpressed in a substantial portion of TNBC, correlating with decreased survival and increased metastasis, making it an attractive therapeutic target.
Purpose of the Study:
- To investigate the efficacy of a bispecific antibody, MesobsFab, targeting mesothelin and engaging CD16 for immunotherapy in TNBC.
- To evaluate the in vitro and in vivo anti-tumor effects of MesobsFab in TNBC models.
Main Methods:
- Utilized two TNBC cell lines with varying MSLN expression and phenotypes.
- Assessed MesobsFab's ability to recruit and activate NK cells, induce cytotoxicity, cytokine secretion, and reduce invasiveness in vitro.
- Evaluated in vivo anti-tumor effects in relation to MSLN density on target cells.
Main Results:
- MesobsFab enhanced NK cell recruitment and penetration into tumor spheroids in vitro.
- Demonstrated potent, dose-dependent cytotoxicity against MSLN-positive TNBC cells, increased cytokine secretion, and reduced invasiveness.
- Confirmed MesobsFab-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) via NK cell-mediated antibody-dependent cell cytotoxicity (ADCC).
- Established that in vivo anti-tumor efficacy is dependent on a threshold of MSLN expression on tumor cells.
Conclusions:
- Mesothelin is a relevant therapeutic target for a subset of TNBC with poor survival outcomes.
- MesobsFab shows potential as an antibody-based immunotherapeutic agent for MSLN-expressing TNBC.
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