Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine.

Neuro-oncology
Connor J LiuGavin P Dunn

Abstract

Although clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed "neoantigens," represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination. Flow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TILs). Whole-exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite, and top-ranking candidates were screened for reactivity by interferon-gamma enzyme linked immunospot assays. Survival analysis was performed comparing neoantigen vaccination, anti-programmed cell death ligand 1 (αPD-L1), or combination therapy. Compared with the GL261 model, CT2A exhibited immunologic features consistent with human GBM including reduced αPD-L1 sensitivity and hypofunctional TILs. Of the 29 CT2A neoantigens screened, we identified neoantigen-specific CD8+ T-cell responses in the intracranial TIL and drain...Continue Reading

References

Jan 7, 2004·Nature Reviews. Cancer·Jeffrey W Pollard
Sep 2, 2004·Nature Medicine·Steven A RosenbergNicholas P Restifo
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Feb 5, 2008·Cancer Research·Neil H SegalJames P Allison
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
Jun 9, 2012·European Journal of Immunology·Mikkel HarndahlSøren Buus
Mar 7, 2013·International Journal of Radiation Oncology, Biology, Physics·Jing ZengMichael Lim
Apr 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Orin BlochAndrew T Parsa
Nov 20, 2014·The New England Journal of Medicine·Alexandra SnyderTimothy A Chan
Aug 11, 2015·The Journal of Clinical Investigation·Matthew M GubinRobert D Schreiber
Sep 12, 2015·Science·Eliezer M Van AllenLevi A Garraway
Sep 17, 2015·Cancer Cell·Jinkuk KimDo-Hyun Nam
Nov 8, 2015·Cancer Immunology Research·David A ReardonGordon J Freeman
Jan 31, 2016·Genome Medicine·Jasreet HundalMalachi Griffith
Mar 24, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric BouffetUri Tabori
May 21, 2016·Science·Erlend StrønenTon N Schumacher
Jun 9, 2016·Nature Genetics·Jiguang WangRaul Rabadan
Nov 3, 2016·Cancer Immunology Research·Douglas B JohnsonChristine M Lovly
Feb 25, 2017·Nature Reviews. Cancer·Mark YarchoanElizabeth M Jaffee
Jul 6, 2017·Nature·Patrick A OttCatherine J Wu
Jan 11, 2018·Scientific Reports·Hiroshi NakashimaE Antonio Chiocca
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karolina WoronieckaPeter E Fecci
Mar 24, 2018·Science·Antoni Ribas, Jedd D Wolchok
Nov 6, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T A ChanS Peters
Nov 15, 2018·Cancer Immunology Research·Dylan T BlahaDavid M Kranz
Dec 7, 2018·Science Translational Medicine·Céline M LaumontClaude Perreault

❮ Previous
Next ❯

Citations

Jul 22, 2020·Neuro-oncology·Karolina Woroniecka, Peter E Fecci
Oct 10, 2020·Cancer Immunology, Immunotherapy : CII·Karin L LeeDuane H Hamilton
Dec 3, 2020·Cancer Immunology Research·Edward F FritschCatherine J Wu
Mar 2, 2021·Expert Opinion on Investigational Drugs·Suangson SupabpholWilliam E Gillanders
Mar 13, 2021·Advanced Drug Delivery Reviews·Carina PeresHelena F Florindo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Related Papers

Annals of Oncology : Official Journal of the European Society for Medical Oncology
L LiWilliam E Gillanders
Experimental Hematology & Oncology
Ming YiKongming Wu
Science Translational Medicine
Nicholas McGranahan, Charles Swanton
© 2021 Meta ULC. All rights reserved