Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo

The Journal of Immunology : Official Journal of the American Association of Immunologists
Hollie J PegramPhillip K Darcy

Abstract

NK cells hold great potential for improving the immunotherapy of cancer. Nevertheless, tumor cells can effectively escape NK cell-mediated apoptosis through interaction of MHC molecules with NK cell inhibitory receptors. Thus, to harness NK cell effector function against tumors, we used Amaxa gene transfer technology to gene-modify primary mouse NK cells with a chimeric single-chain variable fragment (scFv) receptor specific for the human erbB2 tumor-associated Ag. The chimeric receptor was composed of the extracellular scFv anti-erbB2 Ab linked to the transmembrane and cytoplasmic CD28 and TCR-zeta signaling domains (scFv-CD28-zeta). In this study we demonstrated that mouse NK cells gene-modified with this chimera could specifically mediate enhanced killing of an erbB2(+) MHC class I(+) lymphoma in a perforin-dependent manner. Expression of the chimera did not interfere with NK cell-mediated cytotoxicity mediated by endogenous NK receptors. Furthermore, adoptive transfer of gene-modified NK cells significantly enhanced the survival of RAG mice bearing established i.p. RMA-erbB2(+) lymphoma. In summary, these data suggest that use of genetically modified NK cells could broaden the scope of cancer immunotherapy for patients.

References

Dec 1, 1995·European Journal of Immunology·M F van den BroekH Hengartner
May 23, 1998·Annual Review of Immunology·L L Lanier
Sep 24, 1999·Leukemia & Lymphoma·J L CohenD Klatzmann
Feb 27, 2001·Journal of Immunological Methods·Z EshharD G Schindler
Mar 22, 2002·Nature Reviews. Immunology·A Cerwenka, L L Lanier
Nov 5, 2002·Nature Biotechnology·Michael H KershawPatrick Hwu
Apr 16, 2003·The Journal of Experimental Medicine·Martin PrlicStephen C Jameson
Sep 30, 2003·European Journal of Immunology·Robert P A WallinHans-Gustaf Ljunggren
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie P PiechockiWei-Zen Wei
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guido FerlazzoChristian Münz
Mar 23, 2004·Annual Review of Immunology·Wayne M YokoyamaAnthony R French
Jun 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Derek C LenzDirk Homann
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael H KershawPhillip K Darcy
Apr 22, 2005·British Journal of Haematology·Eleanor J CheadleRobert E Hawkins
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jennifer A WestwoodMichael H Kershaw
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoshihiro Hayakawa, Mark J Smyth
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark J SmythYoshihiro Hayakawa
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael H KershawPatrick Hwu
Feb 3, 2007·Current Opinion in Oncology·Loredana RuggeriAndrea Velardi
Feb 3, 2007·The Journal of Clinical Investigation·Claudia WrzesinskiNicholas P Restifo
May 17, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jimmy Tran, Sam K P Kung

❮ Previous
Next ❯

Citations

Nov 4, 2008·European Journal of Immunology·Christopher J ChanMark J Smyth
Mar 13, 2010·Journal of Oncology·Niels HalamaDirk Jaeger
Aug 11, 2010·Cancer Immunology, Immunotherapy : CII·C J SanchezR T Costello
Apr 8, 2010·Archivum Immunologiae Et Therapiae Experimentalis·David Marc Davies, John Maher
Feb 8, 2011·Cancer Metastasis Reviews·Yuting MaLaurence Zitvogel
Nov 15, 2011·Tissue Antigens·D R Shook, D Campana
Oct 10, 2015·Oncoimmunology·Fernando ArandaLorenzo Galluzzi
Jul 21, 2009·Journal of Internal Medicine·T Sutlu, E Alici
Dec 30, 2014·Oncotarget·Lorenzo GalluzziGuido Kroemer
Apr 26, 2016·The Journal of Clinical Investigation·Andreas KupzStefan H E Kaufmann
Apr 9, 2010·Cancer Immunology, Immunotherapy : CII·Hollie J PegramPhillip K Darcy
Dec 17, 2009·Current Opinion in Oncology·Jonathan E BenjaminRobert S Negrin
Jun 14, 2013·Oncoimmunology·Erika VacchelliLorenzo Galluzzi
Jun 28, 2012·Oncoimmunology·Lorenzo GalluzziGuido Kroemer
Dec 17, 2014·Clinical & Translational Immunology·Michael H KershawPhillip K Darcy
Feb 25, 2010·Journal of Leukocyte Biology·Jennifer A Westwood, Michael H Kershaw
Jun 19, 2012·Cellular & Molecular Immunology·Martha LuevanoAurore Saudemont
Oct 15, 2011·Immunotherapy·Anshu Malhotra, Anil Shanker
Jul 23, 2014·Oncoimmunology·Fernando ArandaLorenzo Galluzzi
Aug 5, 2009·Critical Reviews in Clinical Laboratory Sciences·Constantin N BaxevanisMichael Papamichail
May 23, 2018·Journal of Immunology Research·Yingjun XieXuewen Zhang
Jan 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andreas KupzRichard A Strugnell
Sep 7, 2011·Journal of Translational Medicine·Kirsten B J ScholtenErik Hooijberg
Jul 20, 2010·Immunotherapy·Hollie J PegramPhillip K Darcy
Sep 21, 2021·Expert Opinion on Biological Therapy·Mina HosseiniNima Rezaei
Jul 16, 2011·Biochemical and Biophysical Research Communications·Hui HanXi-Sheng Leng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis