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Article ; Online: Identification of an alternative short ARID5B isoform associated with B-ALL survival.

Chalise, Jaya P / Hu, Zunsong / Li, Min / Shepphird, Jennifer K / Gu, Zhaohui / Gyawali, Purnima / Itakura, Keiichi / Larson, Garrett P

Biochemical and biophysical research communications

2024 Volume 703, Page(s) 149659

Abstract: Utilizing RNA sequence (RNA-Seq) splice junction data from a cohort of 1841 B-cell acute lymphoblastic leukemia (B-ALL) patients we define transcriptionally distinct isoforms of ARID5B, a risk-associated gene identified in genome wide association studies ...

Abstract	Utilizing RNA sequence (RNA-Seq) splice junction data from a cohort of 1841 B-cell acute lymphoblastic leukemia (B-ALL) patients we define transcriptionally distinct isoforms of ARID5B, a risk-associated gene identified in genome wide association studies (GWAS), which associate with disease survival. Short (S) and long (L) ARID5B transcripts, which differ in an encoded BAH-like chromatin interaction domain, show remarkable correlation to the isoform splicing pattern. Testing of the ARID5B proximal promoter of the S & L isoforms indicated that both are functionally independent in luciferase reporter assays. Increased short isoform expression is associated with decreased event-free and overall survival. The abundance of short and long transcripts strongly correlates to B-ALL prognostic stratification, where B-ALL subtypes with poor outcomes express a higher proportion of the S-isoform. These data demonstrate that the analysis of independent promoters and alternative splicing events are essential for improved risk stratification and a more complete understanding of disease pathology.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Alternative Splicing ; RNA Splicing ; Base Sequence ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Protein Isoforms ; ARID5B protein, human ; DNA-Binding Proteins ; Transcription Factors
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149659
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Article ; Online: How to choose the best journal for your case report.

Rison, Richard A / Shepphird, Jennifer Kelly / Kidd, Michael R

Journal of medical case reports

2017 Volume 11, Issue 1, Page(s) 198

Abstract: Since the establishment of the Journal of Medical Case Reports in 2006, the number of journals that publish case reports has increased rapidly, and most of these journals are open access. Open access publishing usually requires authors to pay publication ...

Abstract	Since the establishment of the Journal of Medical Case Reports in 2006, the number of journals that publish case reports has increased rapidly, and most of these journals are open access. Open access publishing usually requires authors to pay publication fees while offering the articles online, free of charge, and free of most copyright and licensing restrictions. The movement for open access has gained support in the research community, with the publishers BioMed Central and PLOS ONE becoming leaders in scientific publishing in their number of articles and citations. As the number of open access publishers has exploded, so too has the number of publishers that act in bad faith to profit from the open access model. Simple guidelines have been developed and resources are available to help authors choose a suitable journal for publication of their case reports.
MeSH term(s)	Decision Making ; Humans ; Medical Records ; Open Access Publishing/ethics ; Open Access Publishing/standards ; Peer Review ; Periodicals as Topic/standards
Language	English
Publishing date	2017-07-22
Publishing country	England
Document type	Case Reports ; Editorial
ZDB-ID	2269805-X
ISSN	1752-1947 ; 1752-1947
ISSN (online)	1752-1947
ISSN	1752-1947
DOI	10.1186/s13256-017-1351-y
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Article ; Online: Erratum to: How to choose the best journal for your case report.

Rison, Richard A / Shepphird, Jennifer Kelly / Kidd, Michael R

Journal of medical case reports

2017 Volume 11, Issue 1, Page(s) 287

Language	English
Publishing date	2017-10-05
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2269805-X
ISSN	1752-1947 ; 1752-1947
ISSN (online)	1752-1947
ISSN	1752-1947
DOI	10.1186/s13256-017-1452-7
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Article ; Online: When to write a neurology case report.

Rison, Richard A / Shepphird, Jennifer Kelly / Beydoun, Said R

Journal of medical case reports

2016 Volume 10, Page(s) 92

Abstract: Case report publication has seen a resurgence in recent years as awareness of the value of case reports in clinical medicine has grown. Not all areas of medical research are amenable to large clinical trials. Many topics are better addressed by more ... ...

Abstract	Case report publication has seen a resurgence in recent years as awareness of the value of case reports in clinical medicine has grown. Not all areas of medical research are amenable to large clinical trials. Many topics are better addressed by more detailed descriptions of multi-factorial components that contribute to outcomes, and these are areas where case reports shine. Determining the suitability of a case for publication requires background research and discussion. Writing a case or series reinforces many aspects of the medical training process, and house staff are encouraged to research, write, and submit reports. The medical community benefits in many ways from case reports, from improving individual patient care to guiding future research directions.
MeSH term(s)	Humans ; Journalism, Medical/standards ; Medical Records ; Medical Writing/standards ; Neurology ; Periodicals as Topic
Language	English
Publishing date	2016-04-06
Publishing country	England
Document type	Editorial
ZDB-ID	2269805-X
ISSN	1752-1947 ; 1752-1947
ISSN (online)	1752-1947
ISSN	1752-1947
DOI	10.1186/s13256-016-0868-9
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Article ; Online: Corrigendum: Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.

Mirzaei, Hamid R / Rodriguez, Analiz / Shepphird, Jennifer / Brown, Christine E / Badie, Behnam

Frontiers in immunology

2019 Volume 10, Page(s) 780

Abstract: This corrects the article DOI: 10.3389/fimmu.2017.01850.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2017.01850.].
Language	English
Publishing date	2019-04-17
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00780
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Article ; Online: CAR T cells for brain tumors: Lessons learned and road ahead.

Akhavan, David / Alizadeh, Darya / Wang, Dongrui / Weist, Michael R / Shepphird, Jennifer K / Brown, Christine E

Immunological reviews

2019 Volume 290, Issue 1, Page(s) 60–84

Abstract: Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the ... ...

Abstract	Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19-targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune-based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune-suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune-based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.
MeSH term(s)	Animals ; Antigens, Neoplasm/immunology ; Brain Neoplasms/immunology ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Genetic Engineering ; Humans ; Immunity ; Immunotherapy, Adoptive/methods ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Treatment Outcome
Chemical Substances	Antigens, Neoplasm ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
Language	English
Publishing date	2019-07-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12773
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Article: Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.

Mirzaei, Hamid R / Rodriguez, Analiz / Shepphird, Jennifer / Brown, Christine E / Badie, Behnam

Frontiers in immunology

2017 Volume 8, Page(s) 1850

Abstract: Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic ... ...

Abstract	Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.
Language	English
Publishing date	2017-12-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01850
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Article ; Online: Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy.

Stern, Lawrence A / Gholamin, Sharareh / Moraga, Ignacio / Yang, Xin / Saravanakumar, Supraja / Cohen, Joseph R / Starr, Renate / Aguilar, Brenda / Salvary, Vanessa / Hibbard, Jonathan C / Kalbasi, Anusha / Shepphird, Jennifer K / O'Hearn, James / Garcia, K Christopher / Brown, Christine E

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 33, Page(s) e2112006119

Abstract: IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)-based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic ... ...

Abstract	IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)-based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic malignancies. IL13Rα1, the other binding partner of IL13, is ubiquitously expressed in healthy tissue, raising concerns about the therapeutic window of systemic administration. IL13 mutants with diminished binding affinity to IL13Rα1 were previously generated by structure-guided protein engineering. In this study, two such variants, termed C4 and D7, are characterized for their ability to mediate IL13Rα2-specific response as binding domains for CAR T cells. Despite IL13Rα1 and IL13Rα2 sharing similar binding interfaces on IL13, mutations to IL13 that decrease binding affinity for IL13Rα1 did not drastically change binding affinity for IL13Rα2. Micromolar affinity to IL13Rα1 was sufficient to pacify IL13-mutein CAR T cells in the presence of IL13Rα1-overexpressing cells in vitro. Interestingly, effector activity of D7 CAR T cells, but not C4 CAR T cells, was demonstrated when cocultured with IL13Rα1/IL4Rα-coexpressing cancer cells. While low-affinity interactions with IL13Rα1 did not result in observable toxicities in mice, in vivo biodistribution studies demonstrated that C4 and D7 CAR T cells were better able to traffic away from IL13Rα1+ lung tissue than were wild-type (WT) CAR T cells. These results demonstrate the utility of structure-guided engineering of ligand-based binding domains with appropriate selectivity while validating IL13-mutein CARs with improved selectivity for application to systemic IL13Rα2-expressing malignancies.
MeSH term(s)	Animals ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/methods ; Interleukin-13/genetics ; Interleukin-13/pharmacokinetics ; Interleukin-13/therapeutic use ; Interleukin-13 Receptor alpha2 Subunit/antagonists & inhibitors ; Mice ; Neoplasms/therapy ; Protein Engineering ; Tissue Distribution ; Xenograft Model Antitumor Assays
Chemical Substances	Interleukin-13 ; Interleukin-13 Receptor alpha2 Subunit
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2112006119
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Article: A marriage made in torsional space: using GALAHAD models to drive pharmacophore multiplet searches.

Shepphird, Jennifer K / Clark, Robert D

Journal of computer-aided molecular design

2006 Volume 20, Issue 12, Page(s) 763–771

Abstract: Pharmacophore multiplets are useful tools for 3D database searching, with the queries used ordinarily being derived from ensembles of random conformations of active ligands. It seems reasonable to expect that their usefulness can be augmented by instead ... ...

Abstract	Pharmacophore multiplets are useful tools for 3D database searching, with the queries used ordinarily being derived from ensembles of random conformations of active ligands. It seems reasonable to expect that their usefulness can be augmented by instead using queries derived from single ligand conformations obtained from aligned ligands. Comparisons of pharmacophore multiplet searching using random conformations with multiplet searching using single conformations derived from GALAHAD (a genetic algorithm with linear assignment for hypermolecular alignment of datasets) models do indeed show that, while query hypotheses based on random conformations are quite effective, hypotheses based on aligned conformations do a better job of discriminating between active and inactive compounds. In particular, the hypothesis created from a neuraminidase inhibitor model was more similar to half of 18 known actives than all but 0.2% of the compounds in a structurally diverse subset of the World Drug Index. Similarly, a model developed from five angiotensin II antagonists yielded hypotheses that placed 65 known antagonists within the top 0.1-1% of decoy databases. The differences in discriminating power ranged from 2 to 20-fold, depending on the protein target and the type of pharmacophore multiplet used.
MeSH term(s)	Algorithms ; Angiotensin Receptor Antagonists ; Computer Simulation ; Computer-Aided Design ; Drug Design ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Ligands ; Models, Molecular ; Neuraminidase/antagonists & inhibitors ; Neuraminidase/chemistry
Chemical Substances	Angiotensin Receptor Antagonists ; Enzyme Inhibitors ; Ligands ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2006-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	808166-9
ISSN	1573-4951 ; 0920-654X
ISSN (online)	1573-4951
ISSN	0920-654X
DOI	10.1007/s10822-006-9070-2
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Article: Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R〿2-targeting CAR T cells: an interim analysis.

Wang, Leo / Oill, Angela Taravella / Blanchard, M / Wu, Melody / Hibbard, Jonathan / Sepulveda, Sean / Peter, Lance / Kilpatrick, Julie / Munoz, Margarita / Stiller, Tracey / Shulkin, Noah / Wagner, Jamie / Dolatabadi, Ally / Nisis, Monica / Shepphird, Jennifer / Sanchez, Gabriela / Lingaraju, Chetan / Manchanda, Mishika / Natri, Heini /

Kouakanou, Léonce / Sun, Grace / Oliver-Cervantes, Cheryl / Georges, Joseph / Aftabizadeh, Maryam / Forman, Stephen / Priceman, Saul / Ressler, Julie / Arvanitis, Leonidas / Cotter, Jennifer / D'Apuzzo, Massimo / Tamrazi, Benita / Badie, Behnam / Davidson, Tom / Banovich, Nicholas / Brown, Christine

Research square

2023

Abstract: Outcomes for pediatric brain tumor patients remain poor, and there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. Here, we present interim results from the first six pediatric patients treated on an ongoing phase I ...

Abstract	Outcomes for pediatric brain tumor patients remain poor, and there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. Here, we present interim results from the first six pediatric patients treated on an ongoing phase I clinical trial (NCT04510051) of IL13BBζ-CAR T cells delivered weekly into the lateral cerebral ventricles, identifying clonal expansion of endogenous CAR-negative CD8
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3454977/v1
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