Antibody-drug conjugates (ADCs) have emerged as one of the busiest and most crowded niches within oncology, given their potential to use an antibody to ferry a potent cytotoxic payload toward tumor cells. The class now spans about 15 FDA-approved products, and the segment is growing steadily. Evaluate Pharma projects the ADC category will reach $57 billion by 2032.
The core promise of ADCs is to widen chemotherapy’s therapeutic window by using a tumor-targeting antibody to concentrate a potent cytotoxic payload in cancer cells while limiting exposure to healthy tissue.
“Initially, what we were told was that ADCs are basically targeted chemotherapy. I’m going to put a GPS signal on my beachhead, on my chemotherapy target, and it’s going to zone in just to the tumor cells and release its payload,” said Ken Bloom, MD, head of pathology at Nucleai. The promise essentially is, as Bloom put it, getting “all the benefits of chemotherapy without the toxicity.” But “in practice it’s far trickier than that,” he said. A tumor can look target-positive on a pathology slide while the drug’s cell-surface target is altered or inaccessible, extracellular proteases in the tumor microenvironment can cleave some ADC linkers and release their payload, and cancer cells can use drug-efflux pumps to expel certain released payloads.
That gap between what a pathology assay sees and what an ADC encounters is one of the questions Nucleai is probing with Gilead Sciences. The companies disclosed August 11 that Nucleai has analyzed H&E and IHC whole-slide images from several Gilead clinical studies across multiple oncology indications, linking tissue features with clinical outcomes. The relationship began a few years ago with largely preclinical multiplex immunofluorescence work and has expanded into retrospective analysis of clinical-trial datasets.
