Abstract 3481: Comparative spatial transcriptomic analysis of monoclonal antibodies targeting the same molecule: A comparison between cetuximab and panitumumab

Abstract Background: In recent years, multiple therapeutic monoclonal antibodies have been developed that target the same molecules. Examples include trastuzumab and pertuzumab for HER2, cetuximab (CTX) and panitumumab (PNT) for EGFR, as well as pembrolizumab and nivolumab for PD-1. Currently, comparative studies between different monoclonal antibodies with same target primarily focus on comparing their efficacy, which makes it challenging to discern the factors contributing to their varied effectiveness. In this study, we conducted a comparative analysis of CTX and PNT using integrated data of fluorescence imaging and spatial transcriptomics (ST) to explore their distribution, as well as the associated cell types and genes in tumor tissues. Method: A FaDu cancer cell line, which has high EGFR expression, was used to establish tumor model in BALB/C nude mice. In the tumor model, fluorescence dye-conjugated CTX or PNT was intravenously administered. In vivo fluorescence imaging was conducted at 0, 2, and 40 hours. Tumor tissues at 2 and 40 hours were dissected for drug distribution images and 10X Visium ST. SPADE algorithm [1], CellDART [2], and Stopover analysis [3] were employed for integrative analysis, cell type deconvolution, and topological association of interesting genes. Results: In vivo imaging demonstrated that both antibodies exhibited high tumor uptake at 2 hrs, with further increase observed at 40 hrs post-injection. Initially, CellDART analysis confirmed that in the 2 hrs sample, both CTX and PNT exhibited a distribution similar to cancer cells among the various cell types. However, in the 40 hrs sample, the distribution pattern resembled that of cancer cells and inflammatory macrophages for both antibodies. A stopover analysis revealed a higher concordance between CTX distribution and EGFR expression in both the 2 and 40 hrs samples compared to that of PNT. Lastly, the top 100 up-regulated differentially expressed genes which are highly associated with drug distribution were identified through SPADE analysis. Notably, when we checked the intersection between CTX and PNT administered samples for these genes, there was 83% discordance in the associated genes in the 2 hrs sample and 93% in the 40 hrs sample. Conclusion: In the examination of the distribution patterns of two distinct therapeutic antibodies targeting EGFR within cancer tissues, a notable observation was made: while the cell types exhibited similarity, the associated genes demonstrated divergence, with different degrees of alignment with the intended target. This analytical approach, scrutinizing the distribution of different antibodies within tissue sharing a common target, holds promise as a widely applicable method for elucidating divergent therapeutic effects. References: 1. Nucleic Acids Res, 2021 Jun 49;10:e552. Nucleic Acids Res 2022 Jun 10;50:e57.3. bioRxiv 2022.11.16.516708 Citation Format: Jin Yeong Choi, Jeongbin Park, Myunghyun Lim, Daeseung Lee, Jae Eun Lee, Hongyoon Choi, Hyung-Jun Im. Comparative spatial transcriptomic analysis of monoclonal antibodies targeting the same molecule: A comparison between cetuximab and panitumumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3481.