T cell therapy targeting a public neoantigen in microsatellite instable colon cancer reduces in vivo tumor growth

Oncoimmunology
Else M InderbergG Gaudernack

Abstract

T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance. The transforming growth factor β Receptor II frameshift mutation (TGFβRIImut) is found in Lynch syndrome cancer patients and in approximately 15% of sporadic colorectal and gastric cancers displaying microsatellite instability (MSI). The -1A mutation within a stretch of 10 adenine bases (nucleotides 709-718) of the TGFβRII gene gives rise to immunogenic peptides previously used for vaccination of MSI+ colorectal cancer patients in a Phase I clinical trial. From a clinically responding patient, we isolated a cytotoxic T lymphocyte (CTL) clone showing a restriction for HLA-A2 in...Continue Reading

References

Jun 1, 1986·Journal of Clinical Pathology·J R Jass
May 1, 1996·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·F M MarincolaS A Rosenberg
Jun 8, 2001·International Journal of Cancer. Journal International Du Cancer·M LinnebacherM von Knebel Doeberitz
Nov 1, 2001·Proceedings of the National Academy of Sciences of the United States of America·I SaeterdalG Gaudernack
Jan 5, 2002·Cancer Immunology, Immunotherapy : CII·I SaeterdalG Gaudernack
Feb 6, 2004·Gastroenterology·John M CarethersC Richard Boland
Nov 6, 2004·Blood Cells, Molecules & Diseases·S XueE Morris
May 14, 2005·World Journal of Surgical Oncology·Ayan BanerjeaSina Dorudi
Feb 24, 2006·Cancer Immunology, Immunotherapy : CII·Paal F BrunsvigGustav Gaudernack
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura A JohnsonSteven A Rosenberg
Dec 6, 2006·Cancer Research·Gretchen E LyonsMichael I Nishimura
Apr 9, 2008·Gastroenterology·Yvette SchwitalleMagnus von Knebel Doeberitz
Jan 24, 2009·Familial Cancer·Kristen M DrescherHenry T Lynch
Feb 18, 2009·Cancer Immunology, Immunotherapy : CII·Jon Amund KyteGustav Gaudernack
Mar 20, 2009·Current Opinion in Immunology·Rienk Offringa
Jun 9, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·David TougeronJean-Baptiste Latouche
Mar 31, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daphné A SchmidNathalie Rufer
Apr 30, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy L FrankelRichard A Morgan
Dec 16, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Maria R ParkhurstSteven A Rosenberg
Dec 23, 2010·Cytotherapy·Hilde AlmåsbakAnne-Marie Rasmussen
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayDonald Maxwell Parkin
Apr 21, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily CorseJames P Allison
Dec 2, 2011·PloS One·Sébastien WälchliJohanna Olweus
Feb 5, 2013·Journal of Immunotherapy·Richard A MorganSteven A Rosenberg
Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shi ZhongMichelle Krogsgaard
Jul 23, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liza B JohnPhillip K Darcy
Nov 22, 2014·The Journal of Clinical Investigation·Caroline ArberBarbara Savoldo
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Dec 15, 2015·Seminars in Immunology·Yong-Chen Lu, Paul F Robbins
Jan 26, 2016·The Journal of Clinical Investigation·Matthias LeisegangThomas Blankenstein

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Citations

Dec 19, 2017·Cancer Immunology, Immunotherapy : CII·Else Marit InderbergSébastien Wälchli
Dec 19, 2017·Frontiers in Immunology·Eva Bräunlein, Angela M Krackhardt
Feb 28, 2018·CA: a Cancer Journal for Clinicians·Patrick M BolandC Richard Boland
Jul 22, 2018·The Journal of Pathology·Sidhant SethIan M Frayling
Feb 14, 2018·Applied Immunohistochemistry & Molecular Morphology : AIMM·Gunes GunerAytekin Akyol
Mar 16, 2019·Clinical and Experimental Immunology·Y-R Yu, P-C Ho
Jul 7, 2019·Nature Reviews. Cancer·Christof C SmithJonathan S Serody
Aug 22, 2017·Cellular and Molecular Life Sciences : CMLS·Céline M Laumont, Claude Perreault
May 1, 2019·The EMBO Journal·Theresa E SchnalzgerHenner F Farin
Jan 10, 2020·Cancer Immunology, Immunotherapy : CII·Else Marit Inderberg, Sébastien Wälchli
Sep 8, 2017·Scientific Reports·Even WalsengSébastien Wälchli
Jul 10, 2018·Briefings in Functional Genomics·Qinan YinXuekai Zhu
Jun 20, 2019·Cancer Immunology, Immunotherapy : CII·Nadia MensaliElse Marit Inderberg
Jul 23, 2020·Frontiers in Immunology·Valentina BianchiGeorge Coukos
Jan 10, 2019·World Journal of Gastroenterology : WJG·Sandra WagnerMichael Linnebacher
Sep 1, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Sharon Hutchison, Antonia L Pritchard
Jan 10, 2018·Frontiers in Immunology·Thomas C Wirth, Florian Kühnel
Apr 14, 2019·Blood Advances·Hakan KöksalSébastien Wälchli
Jul 16, 2020·Vaccines·Nurul Ainaa Adilah Rus BakarurrainiNadiah Abu
Feb 6, 2018·Oncoimmunology·Claudia MaletzkiMichael Linnebacher
Feb 7, 2019·Oncoimmunology·Nadia MensaliSébastien Wälchli
Nov 26, 2020·The Journal of Biological Chemistry·Hakan KöksalSébastien Wälchli
Nov 20, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Pierre DillardElse Marit Inderberg
Jan 13, 2021·The Journal of Biological Chemistry·Hakan KöksalSébastien Wälchli
Nov 8, 2019·Seminars in Cancer Biology·Monica BenvenutoRoberto Bei
Jul 9, 2021·Oncoimmunology·Pierre DillardElse Marit Inderberg
Aug 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nadia MensaliSébastien Wälchli

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Methods Mentioned

BETA
Flow cytometry
xenograft
transfection
FCS
PCR
electrophoresis
density gradient centrifugation

Software Mentioned

FlowJo
Living Image
IEDB analysis Consensus
GraphPad Prism
GraphPad

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