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Molecular and functional insight into anti-EGFR nanobody: Theranostic implications for malignancies
Rajan K Tripathy1, Abhay H Pande1
1Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, (Mohali) 160062, Punjab, India.
Abstract:
Targeted therapy and imaging are the most popular techniques for the intervention and diagnosis of cancer. A potential therapeutic target for the treatment of cancer is the epidermal growth factor receptor (EGFR), primarily for glioblastoma, lung, and breast cancer. Over-production of ligand, transcriptional up-regulation due to autocrine/paracrine signalling, or point mutations at the genomic locus may contribute to the malfunction of EGFR in malignancies. This exploit makes use of EGFR, an established biomarker for cancer diagnostics and treatment. Despite considerable development in the last several decades in making EGFR inhibitors, they are still not free from limitations like toxicity and a short serum half-life. Nanobodies and antibodies share similar binding properties, but nanobodies have the additional advantage that they can bind to antigenic epitopes deep inside the target that conventional antibodies are unable to access. For targeted therapy, anti-EGFR nanobodies can be conjugated to various molecules such as drugs, peptides, toxins and photosensitizers. These nanobodies can be designed as novel immunoconjugates using the universal modular antibody-based platform technology (UniCAR). Furthermore, Anti-EGFR nanobodies can be expressed in neural stem cells and visualised by effective fluorescent and radioisotope labelling.
Insights
Targeted cancer therapy utilizes epidermal growth factor receptor (EGFR) inhibitors. Novel nanobodies offer improved targeting for EGFR-expressing cancers like glioblastoma, lung, and breast cancer, overcoming limitations of traditional antibodies.
Area of Science:
- Oncology
- Biotechnology
- Immunology
Background:
- Epidermal growth factor receptor (EGFR) is a key target in glioblastoma, lung, and breast cancer treatment.
- Current EGFR inhibitors face limitations including toxicity and short serum half-life.
- Nanobodies offer advantages over conventional antibodies, accessing unique antigenic epitopes.
Purpose of the Study:
- To explore the potential of anti-EGFR nanobodies for targeted cancer therapy and imaging.
- To investigate the design of novel immunoconjugates using the universal modular antibody-based platform technology (UniCAR).
- To assess the feasibility of expressing anti-EGFR nanobodies in neural stem cells for visualization.
Main Methods:
- Conjugation of anti-EGFR nanobodies to therapeutic payloads (drugs, toxins, photosensitizers).
- Development of novel immunoconjugates via the UniCAR platform.
- Expression of nanobodies in neural stem cells with fluorescent and radioisotope labeling for imaging.
Main Results:
- Anti-EGFR nanobodies demonstrate potential for targeted delivery of therapeutics.
- The UniCAR platform enables modular design of novel anti-EGFR immunoconjugates.
- Neural stem cell expression allows for visualization and potential targeted delivery to the central nervous system.
Conclusions:
- Anti-EGFR nanobodies represent a promising advancement in targeted cancer therapy and diagnostics.
- Nanobody technology, particularly with the UniCAR platform, offers enhanced capabilities for cancer intervention.
- Further research into nanobody-based strategies holds potential for improved cancer treatment outcomes.
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