Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas.

Journal for Immunotherapy of Cancer
Claudia Manuela ArnoneFrancesca Del Bufalo

Abstract

Pediatric high-grade gliomas (pHGGs) are among the most common and incurable malignant neoplasms of childhood. Despite aggressive, multimodal treatment, the outcome of children with high-grade gliomas has not significantly improved over the past decades, prompting the development of innovative approaches. To develop an effective treatment, we aimed at improving the suboptimal antitumor efficacy of oncolytic adenoviruses (OAs) by testing the combination with a gene-therapy approach using a bispecific T-cell engager (BiTE) directed towards the erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2), conveyed by a replication-incompetent adenoviral vector (EphA2 adenovirus (EAd)). The combinatorial approach was tested in vitro, in vivo and thoroughly characterized at a molecular level. After confirming the relevance of EphA2 as target in pHGGs, documenting a significant correlation with worse clinical outcome of the patients, we showed that the proposed strategy provides significant EphA2-BiTE amplification and enhanced tumor cell apoptosis, on coculture with T cells. Moreover, T-cell activation through an agonistic anti-CD28 antibody further increased the activation/proliferation profiles and functional respon...Continue Reading

References

Jan 11, 2003·Cancer Gene Therapy·Tony ReidDavid Kirn
May 19, 2005·Cancer Research·Kathrin Maria BerntAndré Lieber
Nov 19, 2005·Nature Reviews. Cancer·Kelley A ParatoJohn C Bell
Aug 16, 2006·The New England Journal of Medicine·Ganesh SuntharalingamNicki Panoskaltsis
Jan 15, 2008·Journal of Neuro-oncology·Muh-Lii LiangCynthia Hawkins
Jan 23, 2009·Immunobiology·Cornelia HaasPatrick A Baeuerle
Mar 23, 2011·Experimental Cell Research·Dirk Nagorsen, Patrick A Baeuerle
Mar 9, 2012·Advances in Virology·Mark S FergusonYaohe Wang
Oct 17, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kevin K H ChowStephen Gottschalk
Apr 26, 2014·Cancer Immunology Research·E Antonio Chiocca, Samuel D Rabkin
Aug 22, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kota IwahoriStephen Gottschalk
Feb 19, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ignazio CaruanaGianpietro Dotti
Jun 19, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valentina HoyosMalcolm K Brenner
May 19, 2016·Immunity·Jonathan H EsenstenJeffrey A Bluestone
Jul 21, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaozhu LiShengdian Wang
Dec 22, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arend von StackelbergLia Gore
Feb 2, 2017·Cancer Research·Carlos Alberto FajardoRamon Alemany
Aug 20, 2017·Cancer Immunology Research·Mireya Paulina VelasquezStephen Gottschalk
Oct 5, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amanda Rosewell ShawMasataka Suzuki
Oct 11, 2017·Neuro-oncology·Kevin BielamowiczNabil Ahmed
May 8, 2018·Nature Reviews. Cancer·Kwame Twumasi-BoatengBrad H Nelson
Dec 1, 2018·Human Gene Therapy·Yang WangBinlei Liu
Feb 2, 2019·Methods in Molecular Biology·Ekramy E SayedahmedSuresh K Mittal
May 30, 2019·Nature Communications·Naiara Martínez-VélezMarta M Alonso

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Software Mentioned

BioRender
QuantStudio Flex
GraphPad
Prism

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy 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.

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