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.
Curr Pharm Des
; 30(11): 868-876, 2024.
Article
en En
| MEDLINE
| ID: mdl-38482625
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 as an effective agent in the LIV-1-targeted treatment of cancers due to its longer half-life and stronger cytotoxicity.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Interleucina-2
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Curr Pharm Des
Asunto de la revista:
FARMACIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Irán