Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques.
| Title: | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques. |
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| Authors: | 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. |
| Source: | IScience [iScience] 2022 Feb 09; Vol. 25 (3), pp. 103889. Date of Electronic Publication: 2022 Feb 09 (Print Publication: 2022). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, [2018]- |
| Abstract: | 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.; (© 2022 The Authors.) |
| Competing Interests: | Dr. Robert Schaub’s former employment with NKT Therapeutics, the manufacturer of NKTT320, may be considered a potential conflict of interest. |
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| Grant Information: | R24 OD010947 United States OD NIH HHS; U24 AI126683 United States AI NIAID NIH HHS; P51 OD011104 United States OD NIH HHS; R21 OD031229 United States OD NIH HHS; R01 AI102693 United States AI NIAID NIH HHS; R21 AI145642 United States AI NIAID NIH HHS; R01 AI167644 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: Biological sciences; Components of the immune system; Immunology; Transcriptomics |
| Entry Date(s): | Date Created: 20220304 Latest Revision: 20260307 |
| Update Code: | 20260307 |
| PubMed Central ID: | PMC8866157 |
| DOI: | 10.1016/j.isci.2022.103889 |
| PMID: | 35243248 |
| Database: | MEDLINE |
Journal Article