What question did this study set out to answer?

To validate therapeutic antibodies using advanced tools in 3D tumoroid systems for cancer treatment evaluation.

April 5, 2026

Abstract 4447: Next generation molecular tools for evaluating antibody drug conjugates in 3D systems

Key Points

To validate therapeutic antibodies using advanced tools in 3D tumoroid systems for cancer treatment evaluation.
Developed 3D tumoroid models to mimic tumor microenvironments.
Utilized LysoLight tagged antibodies to assess antibody behavior and degradation.
Identified therapeutic candidates through SiteClick rapid antibody conjugation technique.
Conducted high-throughput assays measuring binding affinity and internalization rates.
Evaluated cytotoxic effects of MMAE conjugated antibodies in colon cancer tumoroids.
Higher uptake of Cetuximab observed in EGFR-overexpressing tumoroids compared to EGFR-null tumoroids.
MMAE conjugated antibody-drug conjugate showed targeted cell penetration and induced cell death in colon cancer tumoroids.
Integration of antibody degradation trackers allows for more accurate evaluation of therapeutic efficacy in vivo.

Abstract

Abstract The development of effective anti-cancer drugs relies on accurately evaluating therapeutic antibodies. Three-dimensional (3D) tumoroids, which closely mimic the tumor microenvironment, help provide a promising platform for these evaluations. Our research focuses on validating therapeutics using antibody degradation trackers and antibody drug conjugates within 3D tumoroids. LysoLight tagged antibodies are fluorogenic in lysosomes, allowing visualization of antibody behavior within tumoroids, enabling insights into antibody degradation. Our studies showed higher Cetuximab uptake and localization to lysosomes in EGFR-overexpressing lung adenocarcinoma tumoroids, while non-specific antibodies or EGFR-null tumoroids showed minimal LysoLight activity. Additionally, we generated MMAE conjugated therapeutic antibodies using the new SiteClick rapid antibody conjugation technique, that allowed rapid screening of candidates from selected monoclonal antibodies to identify candidates with favorable therapeutic potential. High-throughput assays within 3D tumoroids enabled us to evaluate binding affinity, internalization rates, and cytotoxic effects. Our findings indicated that a MMAE conjugated EGFR targeted antibody-drug conjugate, facilitated a targeted cell penetration of drugs in colon cancer tumoroids and induced cell death. Integrating antibody degradation trackers and high-throughput Ab screenings within 3D tumoroids offers a robust platform for evaluating therapeutic efficacy, by providing a more accurate representation of their behavior in vivo. Disclaimer: For Research Use Only. Not for use in diagnostic procedures. © 2025 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. Citation Format: Jayanth Surya Narayanan Shankara Narayanan, Ryan Holly. Next generation molecular tools for evaluating antibody drug conjugates in 3D systems abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4447.

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Cite This Study

Narayanan et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fc4fa79560c99a0a1f50 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-4447

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