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


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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.

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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