B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma
Zhiping Zhou,Neal Luther,George M. Ibrahim,Cynthia Hawkins,Rajeev Vibhakar,Rajeev Vibhakar,Michael H. Handler,Michael H. Handler,Mark M. Souweidane,Mark M. Souweidane +9 more
TLDR
B7-H3 is over-expressed in DIPG and given the need for novel treatment in this disease, antibody-based immunotherapy against B7- H3 in D IPG warrants further investigation.Abstract:
Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.read more
Citations
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CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors.
Robbie G. Majzner,Johanna Theruvath,Anandani Nellan,Sabine Heitzeneder,Yongzhi Cui,Christopher Mount,Skyler P. Rietberg,Miles H. Linde,Peng Xu,Christopher Rota,Elena Sotillo,Louai Labanieh,Daniel W. Lee,Rimas J. Orentas,Dimiter S. Dimitrov,Zhongyu Zhu,Brad St. Croix,Alberto Delaidelli,Alberto Delaidelli,Alla Sekunova,Alla Sekunova,Ezio Bonvini,Siddhartha Mitra,Siddhartha Mitra,Martha Quezado,Ravindra Majeti,Michelle Monje,Poul H. Sorensen,Poul H. Sorensen,John M. Maris,Crystal L. Mackall +30 more
TL;DR: B7-H3 CAR T-cell efficacy is largely dependent upon high surface target antigen density on tumor tissues and that activity is greatly diminished against target cells that express low levels of antigen, thus providing a possible therapeutic window despite low-level normal tissue expression of B7- H3.
Journal ArticleDOI
B7 family checkpoint regulators in immune regulation and disease
TL;DR: Recent understanding of B7 family members and their concerted regulation of the immune response to either self or foreign pathogens is reviewed, including clinical developments in targeting these pathways in different disease settings, and VISTA is introduced as a putative therapeutic target.
Journal ArticleDOI
Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial
Mark M. Souweidane,Mark M. Souweidane,Kim Kramer,Kim Kramer,Neeta Pandit-Taskar,Neeta Pandit-Taskar,Zhiping Zhou,Zhiping Zhou,Sofia Haque,Sofia Haque,Pat Zanzonico,Jorge A. Carrasquillo,Jorge A. Carrasquillo,Serge K. Lyashchenko,Serge K. Lyashchenko,Sunitha B. Thakur,Maria Donzelli,Ryan S Turner,Jason S. Lewis,Nai-Kong V. Cheung,Steven M. Larson,Ira J. Dunkel,Ira J. Dunkel +22 more
TL;DR: PET-based dosimetry of the radiolabelled antibody [124I]-8H9 validated the principle of using convection-enhanced delivery in the brain to achieve high intra-lesional dosing with negligible systemic exposure in children with diffuse intrinsic pontine glioma.
Journal ArticleDOI
DIPG in Children – What Can We Learn from the Past?
TL;DR: Recent development of DIPG tumor models should help to accurately identify and validate therapeutic targets and small molecule inhibitors in the treatment of this deadly tumor.
B7-H3 role in the immune landscape of cancer.
Jose R. Castellanos,Ian J Purvis,Collin M. Labak,Maheedhara R. Guda,Andrew J. Tsung,Kiran Kumar Velpula,Swapna Asuthkar +6 more
TL;DR: The roles of B7-H3 in different cancers, its relationship with other immune checkpoints, and its non-immunological function in cancer progression are characterized to lead to improved therapeutic options and better clinical outcomes.
References
More filters
Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
Bioconductor: open software development for computational biology and bioinformatics
Robert Gentleman,Vincent J. Carey,Douglas M. Bates,Benjamin M. Bolstad,Marcel Dettling,Sandrine Dudoit,Byron Ellis,Laurent Gautier,Yongchao Ge,Jeff Gentry,Kurt Hornik,Torsten Hothorn,Wolfgang Huber,Stefano Maria Iacus,Rafael A. Irizarry,Friedrich Leisch,Cheng Li,Martin Maechler,A. J. Rossini,Günther Sawitzki,Colin A. Smith,Gordon K. Smyth,Luke Tierney,Jean Yang,Jianhua Zhang +24 more
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Journal ArticleDOI
R: A Language for Data Analysis and Graphics
Ross Ihaka,Robert Gentleman +1 more
TL;DR: In this article, the authors discuss their experience designing and implementing a statistical computing language, which combines what they felt were useful features from two existing computer languages, and they feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scope.
Journal ArticleDOI
Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit.
TL;DR: The Kw provides for the incorpation of ratio-scaled degrees of disagreement (or agreement) to each of the cells of the k * k table of joi.
Journal ArticleDOI
Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome
Jérôme Galon,Anne Costes,Fátima Sánchez-Cabo,Amos Kirilovsky,Bernhard Mlecnik,Christine Lagorce-Pagès,Marie Tosolini,Matthieu Camus,Anne Berger,Philippe Wind,Franck Zinzindohoué,Patrick Bruneval,Paul-Henri Cugnenc,Zlatko Trajanoski,Wolf H. Fridman,Franck Pagès +15 more
TL;DR: In situ analysis of tumor-infiltrating immune cells may be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.
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