Production and Evaluation of an Avian IgY Immunotoxin against CD133+ for Treatment of Carcinogenic Stem Cells in Malignant Glioma: IgY Immunotoxin for the Treatment of Glioblastoma
| Autor: | Julio Sotelo, Edgar Rangel López, Elda-Georgina Chavez-Cortez, Benjamín Pineda, Gustavo Vargas Felix, Carlos Martínez-Canseco, Verónica Pérez de la Cruz |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Article Subject medicine.medical_treatment lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Antigen Immunotoxin Cancer stem cell Glioma Medicine Cytotoxic T cell neoplasms biology business.industry Immunotherapy medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Antibody Stem cell business Research Article |
| Zdroj: | Journal of Oncology Journal of Oncology, Vol 2019 (2019) |
| ISSN: | 1687-8450 |
| Popis: | Background. Glioblastoma is the most common malignant tumor of Central Nervous System. Despite the research in therapeutics, the prognosis is dismal. Malignant glioma stem cells (MGSCs) are a major cause of treatment failure and increasing tumor recurrence. In general, cancer stem cells (CSCs) express prominin-1 (CD133), considered as a potential therapeutic target. In this study, we produced an avian immunotoxin directed against the subpopulation of CD133+ CSCs within a malignant glioma. We used the avian IgY because it has various advantages as increased affinity to mammal antigens and inexpensive obtention of large amounts of specific antibodies (approximately 1 mg/per egg). The design, production, purification and use of IgY anti CD133 immunotoxin constitute an original goal of this research.Methods. The immunodominant peptide of CD133 was designed to immunize hens; also, the extracellular domain of CD133 was cloned to probe the IgY antibodies. In parallel, a recombinant abrin A chain was produced inE. coliin order to join it to the Fc domain of the anti-CD133 IgY to conform the immunotoxin. This anti-CD133 IgY anti-tumor immunotoxin was testedin vitroandin vivo. Results. The cytotoxicity of the immunotoxinin vitroshowed that IgY-abrin immunotoxin reduced 55% cell viability. After subcutaneous MGSCs implantation, the animals treated intraperitoneally or intratumorally with the IgY-abrin immunotoxin showed more than 50% decrease of tumor volume.Conclusion. Results showed that the IgY-abrin immunotoxin had cytotoxic activity against CD133+ MGSCs and provides a novel approach for the immunotherapy of glioblastoma. |
| Databáze: | OpenAIRE |
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