Dr Tarantino on Understanding the Role of ADC Payloads in Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses the importance of understanding the role that payloadsplay in treatment with antibody-drug conjugates (ADC) in breast cancer.

Regarding novel targets for ADCs, it is vital to recognize that target expression does not represent the entirety of the scenario and that the payload plays a paramount role in thedynamics of the agent, Tarantino begins. The payload facilitates the homing effect of the ADCtoward the tumor and detaches itself from the antibody while circulating in the bloodstream. This detachment contributes to a sustained release of chemotherapy, lending to the efficacy ofthe ADC, he states. Moreover, some of the payloads in specific ADCs can bind with albumin, enabling persistence in circulation, Tarantino explains. Notably, the full extent of the effects ofthe payloads, though substantial, remains incompletely characterized, he adds.

The selection of the antibody and the target are pivotal considerations in ADC development. However, the payload component is equally critical and should not be overlooked, Tarantinocontinues. Emerging data suggest that mechanisms of resistance to ADCs may be linked to both the choice of target and the characteristics of the payload. Tarantino explains that therefore, oncologists should adopt a comprehensive perspective when studying and using ADCs.

Furthermore, the linker holds a key role in determining the stability of the ADC complex, influencing the controlled release of the payload within the tumor microenvironment, Tarantino expands. In drug development, it is essential to explore a wider array of potential targets and diversify the repertoire of payloads, he states. Moreover, refining the linking technology should be a priority. For instance, the success of the DXd platform can be attributed to an innovative linker design that balances intermediate stability, Tarantino notes. This approach allows the payload to reach the tumor while affording broader activity throughout the bloodstream, even in heterogeneous tumors.

As the understanding of ADCs grows, each facet of these agents bears significance in thetreatment of patients, Tarantino concludes.