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Molecular Diagnostics

Anti-PEc: Development of a novel monoclonal antibody against prostate cancer

Abstract

Background

The Ec peptide (PEc) that defines the IGF-1Ec isoform, is associated with prostate cancer progression by inducing proliferation, metastases, and tumour repair. On these grounds, an anti-PEc monoclonal antibody (MAb) was developed. Our objective is to examine the effects of this antibody on prostate cancer and its possible side effects.

Methods

The effects of the obtained MAb were examined in cancer and non-cancerous cell lines (unmodified and modified either to overexpress or silence PEc) and in tumours in SCID mice injected with unmodified prostate cancer cells. The investigation was obtained with respect to cellular proliferation, migration, invasion, toxicity to tumours, effects on the cell cycle, immune response activation, effects on mesenchymal stem cell mobilisation leading to tumour repair, tissue distribution, and toxicity to mice.

Results

Anti-PEc MAb treatment led to a significant decrease in cellular proliferation, migration, and invasion compared to the untreated cell lines (p < 0.0005 in every case). Mechanistically, these effects were associated with the downregulation of pERK1/2 and vimentin and the upregulation of E-Cadherin. In vivo, anti-PEc MAb treatment was associated with a significant decrease in tumour size and metastases rate (p < 0.0005 in every case) by reversing the tumours mesenchymal phenotype. It also inhibited host stem cell mobilisation towards the tumour, leading to apoptosis. Anti-PEc MAb assessment in respect to distribution and toxicity, indicated its tumour specificity and lack of toxicity.

Conclusions

These data indicate that the therapeutic targeting of PEc with the anti-PEc MAb may have considerable clinical benefit for prostate cancer patients.

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Fig. 1: In vitro analysis of the effects of anti-PEc MAb.
Fig. 2: In vivo analysis of the effects of anti-PEc MAb.
Fig. 3: Effects of anti-PEc MAb on tumour repair and survival.
Fig. 4: Determination of the immune mechanism involved in anti-PEc-induced tumour cytotoxicity.
Fig. 5: Effects of anti-PEc MAb treatment on human prostate cancer xenografts.
Fig. 6: Anti-PEc MAb off-target effects and specificity.

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Data availability

1. The proteomics and phosphoproteomics datasets generated during and/or analysed during the current study have been deposited (and are available) to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2019) partner repository with the dataset identifier (title of the paper or the name of the corresponding author). 2. All the rest of the data generated or analysed during this study are included in this published article [and its supplementary information files].

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Acknowledgements

Part of the work of this study was supported by “The Greek Research Infrastructure for Personalised Medicine (pMED-GR)” (MIS 5002802) which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund). We would also like to thank Professors C. Consoulas and C. Palikaras for their useful comments regarding the presentation of the data in the present article.

Funding

This study was financed by the Physiology Laboratory and the National and Kapodestrian University of Athens.

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Authors and Affiliations

Authors

Contributions

AA: Study design, designing and obtaining the constructs, generation of tumours into SCID mice, IF, Ab administration, tumour follow-up, cell culture experiments, writing of the paper. NA: In charge of the clinical part of the study, collection of patient material and clinicopathological characteristics of the patients, MS: Cell culture experiments, tumour removal, sentinel node staining, and removal. CP: Patient immunohistochemistry and evaluation. GA: Animal immunohistochemical analysis and evaluation. MS: Proteomics analysis, phosphoproteomics analysis, GP: Proteomics and phosphoproteomics evaluation, EC: Statistical analysis. MK: Contribution to the study design and in the writing of the paper.

Corresponding author

Correspondence to Athanasios Armakolas.

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The authors declare no competing interests.

Ethics approval and consent to participate

A written informed consent (IC) was obtained from all the patients prior to participation in the present study (attached). The study has been approved by the Institutional Ethics Committee and all the experimental procedures conformed to the Declaration of Helsinki (attached).

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Armakolas, A., Alevizopoulos, N., Stathaki, M. et al. Anti-PEc: Development of a novel monoclonal antibody against prostate cancer. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02713-8

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