A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41067231.
- Also identified by DOI 10.1016/j.xcrm.2025.102409 and PMC identifier 12629802.
- Licence recorded as CC BY-NC-ND.
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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<sup>+</sup> malignant tumor cells, with the production of more cytokines and chemokines. In vivo, tri-NKCE exhibits stronger cytotoxicity by enhancing NK cell proliferation. Compared with chimeric antigen receptor (CAR)-T cells, this tri-NKCE exhibits no toxicity to normal T cells. In conclusion, tri-NKCE offers a safer and cost-effective immunotherapy against T cell malignancies.
Medical subject headings
- Killer Cells, Natural
- Single-Domain Antibodies
- CD5 Antigens