Abstract A028: The evolution of antibody-dye-conjugates: From Ehrlich to immuno-engineering

Abstract The evolution of antibody-dye conjugation and Fc engineering spans more than centuries, mirroring a parallel trajectory of tumor biology and therapeutic resistance. Introduced with Ehrlich’s “Cancer Targeted Therapy” (1897) and “Magic Bullet” concept (1910), successive milestones, from the beginning of the CHO cell line and Mathé’s methotrexate and antigen conjugation in 1957 to the “Golden Era” of Fc engineering in the late 20th century, established the foundation for molecular precision cancer therapeutics. Hybridoma technology, xenograft modeling, and the advent of murine and humanized monoclonal antibodies transformed antibody-drug conjugates (ADCs) into clinically viable platforms. The FDA approval of the first ADC in 2000 for acute lymphocytic leukemia exemplified the translation of evolutionary principles into targeted therapeutics. More recent breakthroughs, including the integration of fluorescent dyes (e.g., Alemtuzumab–Alexa Fluor conjugates), next-generation checkpoint inhibitors (Imatinib, Atezolizumab, Pembrolizumab), and near-infrared fluorophore conjugates, highlight the responsiveness to the challenge posed by tumor heterogeneity, immune evasion, and therapy resistance. This timeline underscores how antibody-dye conjugates have not only advanced cancer detection and therapy but also illustrate the evolutionary arms race between tumors and therapeutic strategies. By drawing their progression through the lens of clonal adaptation and translational innovation, antibody-dye conjugates emerge as both historical benchmarks and future drivers of cancer evolution research. Citation Format: Sdanish Kadir. The evolution of antibody-dye-conjugates: From Ehrlich to immuno-engineering [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr A028 .