Novel SRESPHP peptide mediates specific binding to primary medullary thyroid carcinoma after systemic injection

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Gene therapy faces challenges in specifically targeting cancer cells in vivo.
• Peptides offer potential as tumor-targeting agents for molecular targeting.
• Developing cancer-selective peptides is crucial for reducing off-target effects in gene therapy.

Purpose of the Study:

• To identify novel cancer-selective peptides for targeting medullary thyroid carcinoma (MTC).
• To evaluate the efficacy of identified peptides in directing gene transfer to neoplastic cells.
• To establish a clinically relevant model for MTC targeting using primary murine tumors.

Main Methods:

• Phage display screening was employed on primary orthotopically growing murine MTCs.
• A complex peptide library was intravenously injected into RET-C634R transgenic mice.
• Two rounds of screening identified a phage displaying the cyclic peptide SRESPHP.

Main Results:

• The SRESPHP peptide showed a 3000-fold increase in titer between screening rounds.
• Systemic administration of the phage displayed high tumor specificity, reducing binding to other organs by up to 90%.
• The SRESPHP peptide demonstrated direct binding to MTC tissue in vivo and mediated binding to human MTC cells in vitro and in vivo.

Conclusions:

• The SRESPHP peptide exhibits high specificity and affinity for both murine and human medullary thyroid carcinoma cells.
• Efficient internalization of SRESPHP into MTC cells suggests its potential as a basis for targeted gene therapy.
• This peptide represents a promising new tool for the selective therapy of medullary thyroid carcinoma.