Antibody drug conjugates (ADCs) represent a promising class of anti-cancer drugs combining a monoclonal antibody with a potential cytotoxic agent for selective tumor killing. With many ADCs in clinical trials and over 10 approvals by the U.S. Food and Drug Administration (FDA) since the beginning of this century, it is a rapidly expanding field. Despite this progress, many ADC programs face challenges such as limited efficacy or off-target toxicity, leading to early termination of clinical trials.

At Oncolines, we support ADC development by profiling ADCs and their payloads in our comprehensive cancer cell line panel combined with bioinformatics analyses. This approach enhances understanding of drug responses observed in the clinic. Besides, the choice of relevant cellular models is critical to the success of preclinical studies. Using our receptor quantification assay, we can accurately determine the number of target receptors in each cell line, enabling the selection of the most suitable models for ADC research. Besides, with co-cultures experiments we can study the bystander effects of ADCs.

At the AACR Annual Meeting, we will present cell panel profiling data of trastuzumab emtansine (T-DM1, Kadcyla®), trastuzumab deruxtecan (T-DXd, Enhertu®), their corresponding free payloads, the monoclonal antibody trastuzumab, and small molecule HER2 inhibitor tucatinib. Comparative analyses of the responses of these agents, correlated with HER2 expression levels, provide valuable insights into sensitivity predictors and differentiators.

Our data show that trastuzumab deruxtecan exhibits activity beyond the HER2-positive indication, highlighting its potential in broader tumor types. Moreover, trastuzumab deruxtecan induces a bystander effect in the HER2-negative cell line U-87MG, an effect not observed with trastuzumab emtansine. These findings underscore the importance of understanding ADC mechanisms in diverse cellular contexts to optimize therapeutic efficacy and safety.