ArticleJournal for immunotherapy of cancer2026
From M7824 to SHR-1701: lessons for dual PD-L1/TGF-β targeting.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Retlirafusp alfa (SHR-1701), a bifunctional programmed death-ligand 1 (PD-L1) antibody fused to a TGF-β trap, was approved in China on January 7, 2026 for first-line treatment of PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma with chemotherapy. This first-in-class milestone revisits a key question raised by bintrafusp alfa (M7824): why can dual PD-L1/TGF-β targeting be active in selected settings yet inconsistent across tumors? We highlight that TGF-β-driven immune suppression and immune exclusion are often spatially organized within stromal niches, vary across indications, and are not always the dominant barrier even when PD-L1 is expressed. SHR-1701's approval provides proof of principle in a defined context and supports mechanism-aligned development using biomarker-driven selection, rational combinations and sequencing, and pharmacodynamic endpoints that directly test these assumptions.
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