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Updated: Feb 23, 2026
Syngeneic Mouse Orthotopic Allografts to Model Pancreatic Cancer
Published on: October 4, 2022
A novel inhibitory anti-invasive MAb isolated using phenotypic screening highlights AnxA6 as a functionally relevant
Dermot O'Sullivan1, Paul Dowling2, Helena Joyce1
1National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Background:
Discovery and validation of new antibody tractable targets is critical for the development of new antibody therapeutics to address unmet needs in oncology.
Methods:
A highly invasive clonal variant of the MDA-MB-435S cell line was used to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry. The potential anti-tumour effects of MAb 9E1 were investigated in vitro together with immunohistochemical analysis of the 9E1 target antigen in normal and cancer tissues.
Results:
MAb 9E1 significantly decreases invasion in pancreatic, lung squamous and breast cancer cells and silencing of its target antigen, which was revealed as AnxA6, leads to markedly reduced invasive capacity of pancreatic and lung squamous cancer in vitro. IHC using MAb 9E1 revealed that AnxA6 exhibits a high prevalence of membrane immunoreactivity across aggressive tumour types with restricted expression observed in the majority of normal tissues. In pancreatic ductal adenocarcinoma, high AnxA6 IHC score correlated with the presence of tumour budding at the invasive front of tumours (P=0.082), the presence of perineural invasion (P= <0.0001) and showed a weak correlation with reduced survival (P=0.2242).
Conclusions:
This study highlights the use of phenotypic hybridoma screening as an effective strategy to select a novel function-blocking MAb, 9E1 with anti-cancer activity in vitro. Moreover, through characterisation of the 9E1 target antigen, AnxA6, our findings support further investigation of AnxA6 as a potential candidate target for antibody-mediated inhibition of pancreatic cancer.
Insights
Researchers identified AnxA6 as a novel target for antibody therapy. Monoclonal antibody 9E1 effectively inhibited cancer cell invasion, showing promise for new oncology treatments.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Developing novel antibody therapeutics is crucial for addressing unmet needs in oncology.
- Identifying and validating new antibody-tractable targets is a key step.
Purpose of the Study:
- To discover and characterize a novel antibody target for cancer therapy.
- To evaluate the anti-cancer activity of a function-blocking monoclonal antibody (MAb) 9E1 and its target.
Main Methods:
- Generated monoclonal antibodies (MAbs) using an invasive cancer cell line.
- Screened MAbs for anti-invasive activity and identified the target of MAb 9E1 using mass spectrometry.
- Investigated MAb 9E1 effects in vitro and analyzed target antigen expression via immunohistochemistry (IHC).
Main Results:
- MAb 9E1 significantly reduced invasion in pancreatic, lung, and breast cancer cells.
- The target antigen, Annexin A6 (AnxA6), was identified; its silencing markedly reduced cancer cell invasion.
- AnxA6 showed high membrane expression in aggressive tumors but restricted expression in normal tissues.
- In pancreatic cancer, high AnxA6 expression correlated with perineural invasion and tumor budding.
Conclusions:
- Phenotypic hybridoma screening effectively identified a function-blocking MAb 9E1 with anti-cancer activity.
- AnxA6 is a promising target for antibody-mediated inhibition, particularly in pancreatic cancer.
