A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity.

ABSTRACT: The poor prognosis of patients with recurrent or refractory T cell malignancies emphasizes the need for improved immunotherapies. CD5 is a characteristic marker of malignant T cells and is expressed on almost all normal T cells. Therefore, for treating T cell malignancies, focusing on natural killer (NK) cells lacking CD5 expression may elicit a better safety profile than that by T cell-based therapies. We generate a CD5-targeted NK cell engager (NKCE) through the specific binding of CD16a nanobody and a high-affinity anti-CD5 antibody. Its antitumor potency is demonstrated in vitro. After incorporating interleukin (IL)-15Rα/IL-15, the modified tri-NKCE exhibits stronger antitumor efficacy against CD5⁺ malignant tumor cells, with the production of more cytokines and chemokines.

SUBMITTER: Yang C 

PROVIDER: S-EPMC12629802 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature