Abstract
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 in E. coli in 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 tested in vitro and in vivo. Results. The cytotoxicity of the immunotoxin in vitro showed 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.
Highlights
Glioblastoma is the most common malignant tumor of Central Nervous System
To produce high-affinity antibodies against CD133, we designed an immunogenic peptide inside the extracellular domain of the protein using bioinformatic analysis of CD133 protein
We conducted an in vivo study to determine the effect of IgY-abrin immunotoxin on the tumoral growth in nude mice with Malignant glioma stem cells (MGSCs) of C6 subcutaneously implanted; our results showed a significant decrease in tumor volume when mice were treated with IgY-abrin immunotoxin IP and IT, suggesting that abrin has activity in the induction of apoptosis and inhibiting cell proliferation [51]
Summary
Glioblastoma is the most common malignant tumor of Central Nervous System. Despite the research in therapeutics, the prognosis is dismal. Cancer stem cells (CSCs) express prominin-1 (CD133), considered as a potential therapeutic target. A recombinant abrin A chain was produced in E. coli in 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 tested in vitro and in vivo. Results showed that the IgY-abrin immunotoxin had cytotoxic activity against CD133+ MGSCs and provides a novel approach for the immunotherapy of glioblastoma. Glioblastoma (GBM) is the most frequent primary brain tumor in adulthood and the most aggressive astrocytoma It is characterized by cellular heterogeneity, vascularization, and high capacity to infiltrate. The expression of CD133 on CSCs makes this glycoprotein an adequate target to improve therapeutic efficacy of GBM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
