ArticleJournal for immunotherapy of cancer2026
ROSE12, a novel anti-CTLA-4 FcγRs binding-enhanced antibody activated by extracellular adenosine triphosphate, shows tumor-selective regulatory T-cell depletion and antitumor efficacy without systemic immune activation.
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. It is linked to trial NCT05907980 (A Phase Ia/Ib Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of ROSE12 as a Single Agent and in Combination With Other Anti-tumor Agents in Patients With Locally Advanced or Metastatic Solid Tumors), which is not on this map. Cited by 1 paper.
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A Phase Ia/Ib Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of ROSE12 as a Single Agent and in Combination With Other Anti-tumor Agents in Patients With Locally Advanced or Metastatic Solid Tumors
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1 citing paper in PubMed.
- Next-generation T cell engagers for cancer and autoimmune diseases.Frontiers in immunology · 2026Review
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43 authors.
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Abstract
backgroundIntratumoral regulatory T cells (Tregs) are associated with diminished antitumor immunity and poor prognosis in many cancers, with tumor-infiltrating effector Tregs expressing high levels of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While Treg depletion is a promising strategy for cancer immunotherapy, systemic Treg depletion may lead to severe autoimmune toxicity. Therefore, to selectively deplete intratumoral Tregs, we used extracellular ATP (exATP), which is highly elevated in solid tumors, as a tumor-selective small molecule.
methodsWe generated ROSE12, a novel anti-CTLA-4 Fc gamma receptors (FcγRs)-binding-enhanced-Fc exATP-dependent switch antibody that reduces Tregs only in the presence of exATP. We evaluated ATP-dependent binding affinity, antibody-dependent cellular cytotoxicity (ADCC) activity in vitro, and antitumor efficacy of monotherapy and combination therapy with anti-programmed death-ligand 1 (PD-L1) in CTLA-4/CD3 double humanized mouse models. Safety profiles were assessed in cynomolgus monkeys.
resultsROSE12 demonstrated ATP concentration-dependent binding to CTLA-4, with strong binding at 100 µmol/L but no binding without ATP. ROSE12 demonstrated stronger exATP-dependent ADCC activity in vitro and preferentially reduced CTLA-4
conclusionsThese findings support the clinical development of ROSE12 as a tumor-selective Treg-depleting immunotherapy with potential efficacy in programmed cell death protein-1/PD-L1 therapy-resistant patients. The favorable safety profile was attributed to the ATP-dependent binding mechanism that restricts activity to the high-ATP tumor microenvironment. ROSE12 is currently being evaluated in phase I clinical trials (NCT05907980).
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