CD40L and OX40L

Class

Oncolytic adenovirus (conditionally replicating, CD40L/OX40L-expressing) coated with tumor-associated peptides -- an in-situ personalized cancer vaccine platform; modality field is wrong -- listed as 'small molecule', should be 'oncolytic virus / peptide vaccine'

Pathway

Antigen-specific adaptive immune priming, combined with anti-PD-1 (pembrolizumab)

Notes

original target text: CD40L and OX40L (immune costimulatory ligands expressed by the viral vector); coated with NY-ESO-1 and MAGE-A3 tumor-associated peptides

CD40L (CD154) and OX40L (CD252) are costimulatory ligands normally displayed transiently by activated immune cells to amplify immune responses. CD40L engages CD40 on dendritic cells, driving their maturation and improving their capacity to present antigens to T cells. OX40L engages OX40 on recently activated T cells, extending their survival, promoting clonal expansion, and dampening the suppressive activity of regulatory T cells. In this platform, both ligands are engineered into a conditionally replicating oncolytic adenovirus — a virus modified to multiply selectively within tumor cells and destroy them by lysis. As the virus replicates and kills tumor cells, it releases tumor antigens locally while simultaneously supplying costimulatory signals at the same site, an approach intended to convert a tumor with little pre-existing immune infiltration into one that attracts and sustains an antitumor T-cell response. Coating the viral particles with defined tumor-associated peptides adds known immunogenic targets to this process, and pairing the approach with an antibody blocking the PD-1 checkpoint is meant to prevent the T cells being generated from becoming functionally exhausted. This general strategy, in-situ immune priming combined with checkpoint blockade, is relevant across solid tumors where poor immune infiltration and T-cell exhaustion limit responses to immunotherapy alone.