Fig. 2

Strategies to improve ADC efficacy in pancreatic cancer

Schematic representation of different approaches being undertaken to improve efficacy of ADC therapy in pancreatic cancer. (A) Synergistic interaction between the ADC and immunotherapy may enhance therapeutic response. ADC payloads are known to exhibit immunomodulation through upregulation of co-stimulatory molecules on dendritic cells, which can synergize with checkpoint inhibition to enhance effector T-cell function. (B) Reducing the size of the ADC using nanobody ADCs may help to increase perfusion of the drug into the poorly vascularized and desmoplastic tumor microenvironment (TME) associated with pancreatic cancer. (C) Targeting TME associated antigens may bypass the poor internalization associated with tumor antigens but still allow tumor specific delivery of the payload. (D) Targeting two different mechanisms of cell death by combining ADCs with chemotherapy such as gemcitabine, may help to overcome resistance and improve efficacy compared to either treatment alone. ADC: antibody drug conjugate;CAF: cancer associated fibroblast;DC: dendritic cell;GPC-1: glypican-1;PD-1: programmed cell death protein 1