肿瘤医学与实践杂志

Sensitization of PD-1/L1 Refractory Lung Tumors in an Immunocompetent Mouse Model with AdAPT-001

Abstract

Chris Larson, Bryan Oronsky*, Scott Caroen, Jeannie Williams, Meaghan Stirn and Tony Reid

The reputation of checkpoint inhibitors as potential game changers in oncology is well-deserved as the the 14/14 complete responses recently reported with the PD-1 inhibitor, dostarlimab, in mismatch repair (MMR) deficient locally advanced rectal cancer demonstrates but comes with an important caveat: in most cases and in most cancers non-responders greatly outnumber responders. This begs the question of how to mimic the unprecedented result with dostarlimab in MMR-proficient and otherwise checkpoint inhibitor non-responsive cancers. Several strategies to sensitize tumors to checkpoint inhibitors are under active investigation. These include combinations with other checkpoint inhibitors, chemotherapy, angiogenesis inhibitors, targeted agents, DNA damage repair inhibitors, epigenetic modifiers, and TGF-β inhibitors. This short communication presents data on AdAPT-001, a Type 5 oncolytic adenovirus, currently in a Phase 1/2 clinical trial called BETA PRIME (NCT04673942), which encodes for a transforming growth factor-beta (TGF-β) trap, as an anti-PD-L1 sensitizer.