2024 World Conference on Lung Cancer (WCLC) - Posters-P2.14A.12 Unveiling COL17A1 as a Novel Cell Surface Target in Thymic Epithelial Tumors: A Target Discovery Pipeline Approach

P2.14A.12 Unveiling COL17A1 as a Novel Cell Surface Target in Thymic Epithelial Tumors: A Target Discovery Pipeline Approach

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The study, led by Fatemeh Ardeshir-Larijani and colleagues, presents the discovery of COL17A1 as a promising novel cell surface target in thymic epithelial tumors (TETs), specifically for immune-based therapies. Employing a structured research pipeline, the study aims to identify potential targets to enhance treatment for metastatic TETs, which have historically relied on chemotherapy. <br /><br />This research involved a comprehensive process using both discovery and validation cohorts. The initial phase, or the discovery cohort, used RNA sequencing to analyze transcriptomes from metastatic thymic epithelial tumors (mTETs). Out of a large pool of 60,908 transcripts, ten potential targets were narrowed down, emphasizing those that exhibited high expression in thymomas and thymic carcinoma without significant presence in critical organs. <br /><br />The validation cohort further evaluated these targets through immunohistochemistry (IHC), focusing on proteins such as COL17A1, ABCG1, ANO9, CLDND1, and GRAMD1A. Among these, COL17A1 stood out by showing the highest expression in 66% of TETs, with negligible expression in vital organs. This makes it an ideal candidate for therapies like antibody-drug conjugates (ADC), T-cell engagers, or CAR-T cell therapies. Furthermore, a spatial transcriptomic analysis indicated that COL17A1 exhibits moderate co-localization with T-cell markers, suggesting its potential immunogenic character, which could be crucial for developing immune-based therapies.<br /><br />Overall, the study advances the understanding of potential therapeutic targets in TETs and underscores the viability of COL17A1 as a candidate for future research and development in treatment-resistant thymic epithelial tumors.

Asset Subtitle

Fatemeh Ardeshir Larijani

Meta Tag

Speaker Fatemeh Ardeshir Larijani

Topic Mesothelioma, Thymoma & Other Thoracic Tumors

Keywords

COL17A1

thymic epithelial tumors

TETs

immune-based therapies

metastatic TETs

RNA sequencing

immunohistochemistry

antibody-drug conjugates

CAR-T cell therapies

spatial transcriptomic analysis