Dual targeting OX40 and IL-2 receptor enhances antitumor activity through tumor-infiltrating Treg depletion and CD8⁺ T-cell proliferation.

ABSTRACT:

Background

The strong regulatory T cell (Treg) inhibitory activity and dysfunctional cytotoxic T lymphocytes (CTLs) represent major barriers to effective antitumor immunity, particularly in late-stage cancer. Multiple anti-OX40 (aOX40) agonistic antibodies have been developed but exhibit limited antitumor efficacy. Interleukin-2 (IL-2) effectivity expands CTLs but has severe side effects.

Methods

We construct an aOX40-mIL2-Fc bispecific antibody through Fab physical blocking and attenuated IL-2 with Rβ reducing N88D mutation. We also produced aOX40-Fc and IL-2/aOX40-Fc as a comparison using the 293F expression system. Single-cell and flow cytometry were used to analyze the change of T-cell subsets in the tumor microenvironment (TME). Mouse tumor models were used to assess th

SUBMITTER: Cao S 

PROVIDER: S-EPMC12439149 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature