Specific Targeting of Zinc Transporter LIV-1 with Immunocytokine Containing Anti-LIV-1 VHH and Human IL-2 and Evaluation of its In vitro Antitumor Activity
- Authors: Dehghan R.1, Parikhani A.1, Cohan R.2, Shokrgozar M.3, Mirabzadeh E.4, Ajdary S.5, Zeinali S.4, Ghaderi H.1, Talebkhan Y.6, Behdani M.1
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Affiliations:
- Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran
- Department of Nanobiotechnology,, New Technologies Research Group, Pasteur Institute of Iran
- National Cell Bank of Iran, Pasteur Institute of Iran
- Department of Molecular Medicine, Pasteur Institute of Iran
- Department of Immunology, Pasteur Institute of Iran
- Department of Medical Biotechnology, Biotechnology Research Center,, Pasteur Institute of Iran
- Issue: Vol 30, No 11 (2024)
- Pages: 868-876
- Section: Immunology, Inflammation & Allergy
- URL: https://vestnikugrasu.org/1381-6128/article/view/645500
- DOI: https://doi.org/10.2174/0113816128295195240305060103
- ID: 645500
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Full Text
Abstract
Background:Interleukin 2 (IL-2) is a vital cytokine in the induction of T and NK cell responses, the proliferation of CD8+ T cells, and the effective treatment of human cancers, such as melanoma and renal cell carcinoma. However, widespread use of this cytokine is limited due to its short half-life, severe toxicity, lack of specific tumor targeting, and activation of Treg cells mediated by high-affinity interleukin-2 receptors.
Objective:In this study, a tumor-targeting LIV-1 VHH-mutIL2 immunocytokine with reduced CD25 (α chain of the high-affinity IL-2 receptor) binding activity was developed to improve IL-2 half-life by decreasing its renal infiltration in comparison with wild and mutant IL-2 molecules.
Methods:The recombinant immunocytokine was designed and expressed. the biological activity of the purified fusion protein was investigated in in vitro and in vivo experiments
Results:The fusion protein represented specific binding to MCF7 (the breast cancer cell line) and more efficient cytotoxicity than wild-type IL-2 and mutant IL-2. the PK parameters of the recombinant immunocytokine were also improved in comparison to the IL-2 molecules.
Conclusion:The observed results showed that LIV1-mIL2 immunocytokine could be considered an effective agent in the LIV-1-targeted treatment of cancers due to its longer half-life and stronger cytotoxicity.
Keywords
About the authors
Rada Dehghan
Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran
Email: info@benthamscience.net
Arezoo Parikhani
Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran
Email: info@benthamscience.net
Reza Cohan
Department of Nanobiotechnology,, New Technologies Research Group, Pasteur Institute of Iran
Email: info@benthamscience.net
Mohammad Shokrgozar
National Cell Bank of Iran, Pasteur Institute of Iran
Email: info@benthamscience.net
Esmat Mirabzadeh
Department of Molecular Medicine, Pasteur Institute of Iran
Email: info@benthamscience.net
Soheila Ajdary
Department of Immunology, Pasteur Institute of Iran
Email: info@benthamscience.net
Sirous Zeinali
Department of Molecular Medicine, Pasteur Institute of Iran
Email: info@benthamscience.net
Hajarossadat Ghaderi
Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran
Email: info@benthamscience.net
Yeganeh Talebkhan
Department of Medical Biotechnology, Biotechnology Research Center,, Pasteur Institute of Iran
Author for correspondence.
Email: info@benthamscience.net
Mahdi Behdani
Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran
Author for correspondence.
Email: info@benthamscience.net
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