Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques.

Autor:	Bond NG; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Fahlberg MD; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Yu S; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Rout N; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Tran D; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Fitzpatrick-Schmidt T; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Sprehe LM; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Scheef EA; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Mudd JC; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA., Schaub R; RGS Consulting, Pelham, NH 03076, USA., Kaur A; Tulane National Primate Research Center, Division of Immunology, Covington, LA 70433, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Feb 09; Vol. 25 (3), pp. 103889. Date of Electronic Publication: 2022 Feb 09 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.103889
Abstrakt:	Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic. Competing Interests: Dr. Robert Schaub’s former employment with NKT Therapeutics, the manufacturer of NKTT320, may be considered a potential conflict of interest. (© 2022 The Authors.)
Databáze:	MEDLINE
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