Abstract 16P
Background
Small Cell Lung Cancer (SCLC) is a highly aggressive neuroendocrine cancer with a 5-year survival rate below 5%. Current chemotherapy treatments are limited by toxicity and lack specificity, necessitating targeted approaches. Peptide-drug conjugates (PDCs) are emerging as promising cancer therapies due to their biocompatibility, tumor penetration, and ability to deliver cytotoxic agents. SCLC-specific PDCs are yet to be developed. This study aims to create PDCs using SCLC-specific peptides identified via Phage display, offering a novel, low-toxicity treatment approach.
Methods
SCLC-specific peptides were validated for binding using immunofluorescence and flow cytometry on SCLC cell lines (H146, H69, H889, and H209), confirming selectivity for cancer cells. Stability was assessed via Sephadex-G chromatography and LC-MS in various media, demonstrating minimal degradation. Toxicity was evaluated In vivo by administering PDCs intravenously to mice and monitoring food intake, body weight, and behavior for 12 days.
Results
PDCs showed high specificity to SCLC cells with minimal binding to non-cancerous cells. Stability assays confirmed structural integrity in biological media, with LC-MS showing minimal degradation. In vivo, PDCs exhibited significantly reduced toxicity compared to the drug alone. Mice treated with PDCs maintained normal behavior and weight, while those receiving the drug alone showed pronounced toxicity and increased mortality.
Conclusions
This study highlights PDCs as a targeted, low-toxicity treatment for SCL. SCLC-specific peptides demonstrated strong tumor selectivity and stability, and PDCs reduced drug toxicity while maintaining efficacy. These findings support further In vivo studies and the development of PDC-based therapies for SCLC, offering improved outcomes for patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Michael Firer.
Funding
Ministry of Innovation.
Disclosure
All authors have declared no conflicts of interest.