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.

ABSTRACT:

Background

Intratumoral 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.

Methods

We 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, ant

SUBMITTER: Hayashi H 

PROVIDER: S-EPMC12815072 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature