The development of new, clinically-effective Antibody Drug Conjugates (ADCs) has been hampered by a lack of suitable target antigens, particularly those which target both cancer and cancer-supporting stromal cells.  Oncofetal chondroitin sulfate (ofCS) is an attractive target in this regard, as it is not only broadly expressed across many solid tumors while being largely absent from healthy adult tissues, but also because it enables selective targeting of both cancer cells and tumor stroma. 

In this study, we evaluated two clinically validated linker-payloads with bystander effect: vc–MMAE and ggfg–DXd. Vartumab ADCs using either linker-payload maintained specificity to ofCS, and showed strong and specific tumor uptake in animals. Both ADCs display potent anti-tumor activities. Importantly, ADCs equipped with membrane-permeable payloads induced efficient bystander killing, eliminating not only antigen-positive cancer cells but also antigen-negative tumor cells (genetic knockout). Repeat dosing of Vartumab ADC bearing the vc-MMAE linker payload in rats up to 5 mg/kg showed similar dose limiting toxicities to clinically approved MMAE-conjugated ADCs.

 These findings further strengthen ofCS as a pan-cancer target, and provide a strong preclinical rationale for advancing Vartumab-based ADCs into clinical development.

 Read the full publication here: https://www.nature.com/articles/s41419-026-08420-x