DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy

The Journal of Immunology : Official Journal of the American Association of Immunologists
Katrin TöpferAchim Temme

Abstract

NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment of chimeric Ag receptors (CARs) in NK cells is a promising strategy to redirect NK cells to otherwise NK cell-resistant tumor cells. On the basis of DNAX-activation protein 12 (DAP12), a signaling adaptor molecule involved in signal transduction of activating NK cell receptors, we generated a new type of CAR targeting the prostate stem cell Ag (PSCA). We demonstrate in this article that this CAR, designated anti-PSCA-DAP12, consisting of DAP12 fused to the anti-PSCA single-chain Ab fragment scFv(AM1) confers improved cytotoxicity to the NK cell line YTS against PSCA-positive tumor cells when compared with a CAR containing the CD3ζ signaling chain. Further analyses revealed phosphorylation of the DAP12-associated ZAP-70 kinase and IFN-γ release of CAR-engineered cells after contact with PSCA-positive target cells. YTS cells modified with DAP12 alone or with a CAR bearing a phosphorylation-defective ITAM were not activated. Notably, infused YTS cells armed with anti-PSCA-DAP12 caused delayed tumor xenograft growth and resulted in complete tumor eradication in a significant fraction of treated mice. The feasibility of the DAP...Continue Reading

References

Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M ColonnaJ L Strominger
Feb 17, 1997·The Journal of Experimental Medicine·A G BrooksJ E Coligan
Jan 16, 1998·Immunity·M UhrbergP Parham
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·R E ReiterO N Witte
Jul 9, 1998·Immunity·L L LanierJ H Phillips
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·A B BakkerL L Lanier
Apr 15, 2000·Seminars in Immunology·E O Long, S Rajagopalan
Jul 19, 2000·Current Biology : CB·D N BurshtynE O Long
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·D C SaffranA Jakobovits
Oct 29, 2002·International Journal of Cancer. Journal International Du Cancer·Andrea KiesslingErnst Peter Rieber
Dec 20, 2003·The EMBO Journal·Lorenzo Moretta, Alessandro Moretta
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kerry S CampbellTracey L Catina
Jan 30, 2004·International Journal of Cancer. Journal International Du Cancer·Jan Alvar LindencronaRolf Kiessling
May 27, 2004·European Journal of Immunology·Pokrath HansasutaVeronique M Braud
Aug 12, 2004·Blood·Mónica GumáMiguel López-Botet
Dec 21, 2004·Molecular Immunology·Mark J SmythYoshihiro Hayakawa
Apr 9, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John S LamRobert E Reiter
May 17, 2005·Nature Immunology·Jessica A HamermanLewis L Lanier
Apr 14, 2006·Cancer Immunology, Immunotherapy : CII·Ying Waeckerle-MenSilke Gillessen
Aug 19, 2006·Seminars in Cancer Biology·Loredana RuggeriAndrea Velardi
Sep 2, 2006·Science·Richard A MorganSteven A Rosenberg
Sep 16, 2006·International Journal of Cancer. Journal International Du Cancer·Anna-K Thomas-KaskelHendrik Veelken
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·William H CarrLewis L Lanier
Jan 16, 2007·Nature Reviews. Immunology·Isaiah R Turnbull, Marco Colonna
Mar 12, 2008·The Journal of Experimental Medicine·Emma J PetrieJamie Rossjohn
Apr 22, 2008·Nature Immunology·Lewis L Lanier
Jul 16, 2008·European Journal of Immunology·Mariella Della ChiesaMassimo Vitale
Jul 25, 2008·Blood·Taco W KuijpersEddy Roosnek
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Steven A Rosenberg
Nov 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anna KruschinskiJehad Charo
Feb 24, 2009·Current Opinion in Immunology·Jill W Ford, Daniel W McVicar
Mar 31, 2009·Current Opinion in Immunology·Michel SadelainIsabelle Rivière

❮ Previous
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Citations

Mar 26, 2016·Frontiers in Immunology·Nicolas DulphyAntoine Toubert
May 28, 2016·Molecular Therapy Oncolytics·Daniel Abate-Daga, Marco L Davila
Jun 3, 2016·Expert Review of Anticancer Therapy·Nicole A P LiebermanCourtney A Crane
Jun 7, 2017·Expert Opinion on Biological Therapy·Robyn A A Oldham, Jeffrey A Medin
Jan 13, 2018·Human Gene Therapy·Dennis C HarrerNiels Schaft
Feb 17, 2018·Cell Death & Disease·Maria Michela D'AloiaMaurizio Alimandi
Dec 24, 2015·Nature Reviews. Cancer·Maelig G Morvan, Lewis L Lanier
Jun 20, 2019·International Journal of Molecular Sciences·Ramona RotoloDario Sangiolo
Aug 16, 2019·Physiological Reviews·Carla Riera-DomingoMassimiliano Mazzone
Sep 4, 2019·The Journal of Clinical Investigation·Jonathan J HodginsMichele Ardolino
Jul 18, 2019·Immunology·Lukman O AfolabiXiaochun Wan
Sep 11, 2019·Journal for Immunotherapy of Cancer·Shiran HoogiCyrille J Cohen
May 28, 2020·Cancers·Benjamin MotaisJuli R Bagó
Jul 30, 2020·Expert Opinion on Biological Therapy·Mariya LazarovaAlexander Steinle
Jan 13, 2018·Expert Review of Neurotherapeutics·Nicole A P LiebermanCourtney A Crane
Mar 3, 2018·Frontiers in Immunology·Rohtesh S Mehta, Katayoun Rezvani
Mar 22, 2019·Archives of Pharmacal Research·Nayoung KimHun Sik Kim
Mar 7, 2020·Frontiers in Immunology·Cai ZhangChongdeng Shi
Sep 22, 2015·Current Opinion in Hematology·Yinmeng YangTerry J Fry
Sep 29, 2015·Current Opinion in Organ Transplantation·Melissa M Berrien-ElliottTodd A Fehniger
Mar 20, 2019·Journal of Labelled Compounds & Radiopharmaceuticals·Claudia ArndtStefanie Koristka
Mar 13, 2020·Molekuliarnaia biologiia·G V KochnevaS V Kulemzin
Apr 27, 2019·Frontiers in Oncology·Shabnum PatelConrad Russell Y Cruz
Sep 23, 2019·Cancer Immunology, Immunotherapy : CII·Anja FeldmannMichael P Bachmann
Oct 19, 2019·Journal of Clinical Medicine·Simona SivoriDaniela Pende
Mar 21, 2020·Cancers·Aline Pfefferle, Nicholas D Huntington
Nov 21, 2020·British Journal of Haematology·Hind RafeiKatayoun Rezvani
Dec 9, 2020·Journal of Hematology & Oncology·Ahmet YilmazJianhua Yu
Dec 17, 2020·Vaccines·Piamsiri SawaisornSuradej Hongeng
Apr 24, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel A BurgaCatherine M Bollard
Sep 22, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yu-Yang NgShu Wang
Jan 5, 2021·Frontiers in Immunology·Simone MantessoLucia Kučerová
Oct 3, 2020·Transplantation and Cellular Therapy·Carlos E SanchezConrad Russell Y Cruz
Dec 4, 2019·Cancer Letters·Wenxiu WangChangping Wu

❮ Previous
Next ❯

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