LOAd703 + chemotherapy

**LOAd703 + chemotherapy** is an investigational combination therapy under clinical evaluation primarily for advanced pancreatic ductal adenocarcinoma. LOAd703 is an oncolytic adenovirus engineered to express two immunostimulatory transgenes—trimerized, membrane-bound CD40 ligand (CD40L) and 4-1BB ligand (4-1BBL)—which target and modulate the tumor microenvironment. Upon intratumoral injection, LOAd703 selectively replicates in tumor cells, causing their lysis (oncolysis). The expressed CD40L activates dendritic cells and promotes T cell responses, while 4-1BBL augments T cell survival, proliferation, and effector function. The combination with chemotherapy (most commonly nab-paclitaxel plus gemcitabine) leverages both the cytotoxic effects of chemotherapy and the immunostimulatory, oncolytic mechanisms of LOAd703, aiming to improve immune-mediated tumor clearance. Preclinical and early clinical data suggest this approach is feasible and safe, with signs of immune activation and preliminary clinical activity[1][3][4][5][7].