Download
00262_2024_Article_3835.pdf 1,87MB
WeightNameValue
1000 Titel
  • INTASYL self-delivering RNAi decreases TIGIT expression, enhancing NK cell cytotoxicity: a potential application to increase the efficacy of NK adoptive cell therapy against cancer
1000 Autor/in
  1. Maxwell, Melissa |
  2. Yan, Dingxue |
  3. Rivest, Brianna |
  4. Boone, Andrew |
  5. Cardia, James |
  6. Noessner, Elfriede |
1000 Verlag
  • Springer Berlin Heidelberg
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-10-03
1000 Erschienen in
1000 Quellenangabe
  • 73(12):239
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00262-024-03835-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447204/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Natural killer (NK) cells are frontline defenders against cancer and are capable of recognizing and eliminating tumor cells without prior sensitization or antigen presentation. Due to their unique HLA mismatch tolerance, they are ideal for adoptive cell therapy (ACT) because of their ability to minimize graft-versus-host-disease risk. The therapeutic efficacy of NK cells is limited in part by inhibitory immune checkpoint receptors, which are upregulated upon interaction with cancer cells and the tumor microenvironment. Overexpression of inhibitory receptors reduces NK cell-mediated cytotoxicity by impairing the ability of NK cells to secrete effector cytokines and cytotoxic granules. T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), a well-known checkpoint receptor involved in T-cell exhaustion, has recently been implicated in the exhaustion of NK cells. Overcoming TIGIT-mediated inhibition of NK cells may allow for a more potent antitumor response following ACT. Here, we describe a novel approach to TIGIT inhibition using self-delivering RNAi compounds (INTASYL™) that incorporates the features of RNAi and antisense technology. INTASYL compounds demonstrate potent activity and stability, are rapidly and efficiently taken up by cells, and can be easily incorporated into cell product manufacturing. INTASYL PH-804, which targets TIGIT, suppresses TIGIT mRNA and protein expression in NK cells, resulting in increased cytotoxic capacity and enhanced tumor cell killing in vitro. Delivering PH-804 to NK cells before ACT has emerged as a promising strategy to counter TIGIT inhibition, thereby improving the antitumor response. This approach offers the potential for more potent off-the-shelf products for adoptive cell therapy, particularly for hematological malignancies.
1000 Sacherschließung
lokal RNAi
lokal Cell Line, Tumor [MeSH]
lokal Humans [MeSH]
lokal NK cells
lokal Neoplasms/immunology [MeSH]
lokal Receptors, Immunologic/genetics [MeSH]
lokal Cytotoxicity, Immunologic [MeSH]
lokal Killer Cells, Natural/transplantation [MeSH]
lokal RNA Interference [MeSH]
lokal RNA, Small Interfering/genetics [MeSH]
lokal TIGIT
lokal Research
lokal Adoptive cell therapy (ACT)
lokal Killer Cells, Natural/immunology [MeSH]
lokal Neoplasms/therapy [MeSH]
lokal Receptors, Immunologic/immunology [MeSH]
lokal Immunotherapy, Adoptive/methods [MeSH]
lokal Receptors, Immunologic/metabolism [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0009-0006-7383-071X|https://frl.publisso.de/adhoc/uri/WWFuLCBEaW5neHVl|https://frl.publisso.de/adhoc/uri/Uml2ZXN0LCBCcmlhbm5h|https://frl.publisso.de/adhoc/uri/Qm9vbmUsIEFuZHJldw==|https://frl.publisso.de/adhoc/uri/Q2FyZGlhLCBKYW1lcw==|https://frl.publisso.de/adhoc/uri/Tm9lc3NuZXIsIEVsZnJpZWRl
1000 Hinweis
  • DeepGreen-ID: 769fca7e4948447d9f4f9548c481aa29 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6523854.rdf
1000 Erstellt am 2025-07-07T00:28:50.819+0200
1000 Erstellt von 322
1000 beschreibt frl:6523854
1000 Zuletzt bearbeitet 2025-07-29T20:49:15.899+0200
1000 Objekt bearb. Tue Jul 29 20:49:15 CEST 2025
1000 Vgl. frl:6523854
1000 Oai Id
  1. oai:frl.publisso.de:frl:6523854 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source