2024 World Conference on Lung Cancer (WCLC) - Posters-P2.11A.02 Proteomics-Based Target Identification for Optimizing Bispecific Antibody Use in NSCLC

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The study focuses on proteomics-based target identification to optimize the use of bispecific antibodies (BsAbs) in non-small cell lung cancer (NSCLC), specifically in lung adenocarcinoma (LUAD). BsAbs are engineered to bind two distinct antigens, enhancing immune responses against cancer cells, and are used in treating various malignancies, including primary LUAD.<br /><br />Using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database, researchers assessed 110 primary LUAD samples and 101 normal lung tissue controls to analyze the expression of tumor-associated antigens (TAAs) targeted by BsAbs in development. The study analyzed the expression of proteins such as MET, EGFR, PD-L1, and many others using TMT 10-plex isobaric labeling and LC-MS/MS. Hierarchical clustering of these samples uncovered five distinct patterns of BsAb target antigen expression among the tumors. These patterns include overexpression in CEACAM5, MS4A1 with CD3E, B7H3, MET, and EPCAM.<br /><br />The study also found notable mutual exclusivity, particularly between the overexpression of CEACAM5, MS4A1, and PDL1. This suggests that biomarker-guided strategies could optimize BsAb selection, potentially aiding in the rational design of BsAbs for lung adenocarcinoma treatment.<br /><br />The findings emphasize the importance of targeting proteomic signatures to enhance the efficacy and development of BsAbs in cancer therapy, specifically in lightening tumor intertumoral heterogeneity. These insights could guide drug development and improve the targeting of bispecific antibodies in personalized cancer treatment strategies for LUAD. <br /><br />The study was conducted by a collaboration of researchers from different institutions including Corewell Health William Beaumont University Hospital, Mayo Clinic, St. Vincent Hospital, and the University of Alabama at Birmingham.

Asset Subtitle

Atulya Khosla

Meta Tag

Speaker Atulya Khosla

Topic Metastatic NSCLC – Immunotherapy

Keywords

proteomics

bispecific antibodies

non-small cell lung cancer

lung adenocarcinoma

tumor-associated antigens

Clinical Proteomic Tumor Analysis Consortium

CEACAM5

biomarker-guided strategies

tumor intertumoral heterogeneity

personalized cancer treatment