Abstract 2155: Phage display discovery of Trop-2 peptide for targeted liposomal chemo-immunotherapy in lung cancer

Abstract Background: Lung cancer remains a leading cause of cancer-related mortality worldwide. Targeted therapies offer a promising approach to improve treatment efficacy and reduce systemic toxicity. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is overexpressed in multiple cancers including lung cancer. Trop-2 is an ideal candidate for targeted therapy of NSCLC as it is highly expressed in NSCLC in comparison to normal cells and it is a transmembrane protein with an extracellular domain that can be targeted by therapies. Recently various Trop-2-targeted therapies have been investigated in clinical trials, including anti-Trop-2 antibodies and Trop-2-targeted antibody-drug conjugates (ADC). This study aims to discover a Trop-2 specific peptide using phage display biopanning and develop a liposomal formulation surface-modified with the identified peptide for targeted chemo-immunotherapy. Methods: A peptide phage display library was screened to identify peptides with high affinity for Trop-2 protein. The selected Trop-2 peptide was conjugated to the surface of liposomes encapsulating cisplatin and anti-PDL1 single-chain variable fragment (scFv). The targeting efficiency, cytotoxicity, and immunomodulatory effects of the Trop-2 peptide-modified liposomes were evaluated in vitro using A549 lung cancer cell lines and in vivo in Calu-3 NSCLC xenograft model. Results: The phage display biopanning successfully identified a high-affinity Trop-2 peptide. Liposomes modified with this peptide demonstrated enhanced binding and uptake by A549 lung cancer cells compared to non-targeted liposomes. In vivo, the targeted liposomal formulation exhibited superior tumor growth inhibition and prolonged survival in the Calu-3 NSCLC xenograft model. Conclusion: The discovery of a Trop-2 specific peptide via phage display and its application in targeted liposomal delivery of cisplatin and anti-PDL1 scFv represents a novel and effective strategy for lung cancer chemo-immunotherapy. This approach holds potential for improving therapeutic outcomes and minimizing adverse effects in lung cancer patients. Citation Format: Bahaa S. Mustafa, Bolni M Nagalo, Mulu Tesfay, Usran Khandoker Ferdous, Aleksandra Cios. Phage display discovery of Trop-2 peptide for targeted liposomal chemo-immunotherapy in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2155.