Read by QxMD icon Read

Carl H June

Francisco Vaz-Guimaraes, Maria Koutourousiou, John R de Almeida, Elizabeth C Tyler-Kabara, Juan C Fernandez-Miranda, Eric W Wang, Carl H Snyderman, Paul A Gardner
OBJECTIVE Epidermoid and dermoid cysts may be found along the cranial base and are commonly resected via open transcranial approaches. The use of endoscopic endonasal approaches for resection of these tumors has been rarely reported. METHODS The authors retrospectively reviewed the medical records of 21 patients who underwent endoscopic endonasal surgery for epidermoid and dermoid cyst resection at the University of Pittsburgh Medical Center between January 2005 and June 2014. Surgical outcomes and variables that might affect the extent of resection and complications were analyzed...
March 16, 2018: Journal of Neurosurgery
Stephen J Bagley, Arati S Desai, Gerald P Linette, Carl H June, Donald M O'Rourke
In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T cell therapy for glioblastoma. In addition, despite formidable barriers to T cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients...
March 2, 2018: Neuro-oncology
Mireia Uribe-Herranz, Kyle Bittinger, Stavros Rafail, Sonia Guedan, Stefano Pierini, Ceylan Tanes, Alex Ganetsky, Mark A Morgan, Saar Gill, Janos L Tanyi, Frederic D Bushman, Carl H June, Andrea Facciabene
Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response...
February 22, 2018: JCI Insight
Shannon L Maude, Theodore W Laetsch, Jochen Buechner, Susana Rives, Michael Boyer, Henrique Bittencourt, Peter Bader, Michael R Verneris, Heather E Stefanski, Gary D Myers, Muna Qayed, Barbara De Moerloose, Hidefumi Hiramatsu, Krysta Schlis, Kara L Davis, Paul L Martin, Eneida R Nemecek, Gregory A Yanik, Christina Peters, Andre Baruchel, Nicolas Boissel, Francoise Mechinaud, Adriana Balduzzi, Joerg Krueger, Carl H June, Bruce L Levine, Patricia Wood, Tetiana Taran, Mimi Leung, Karen T Mueller, Yiyun Zhang, Kapildeb Sen, David Lebwohl, Michael A Pulsipher, Stephan A Grupp
BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL...
February 1, 2018: New England Journal of Medicine
Catharina Steentoft, Denis Migliorini, Tiffany R King, Ulla Mandel, Carl H June, Avery D Posey
Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower. Solid tumors are characterized by a number of challenges that need to be overcome, including cellular heterogeneity, immunosuppressive tumor microenvironment (TME), and, in particular, few known cancer-specific targets...
January 23, 2018: Glycobiology
Sonia Guedan, Avery D Posey, Carolyn Shaw, Anna Wing, Tong Da, Prachi R Patel, Shannon E McGettigan, Victoria Casado-Medrano, Omkar U Kawalekar, Mireia Uribe-Herranz, Decheng Song, J Joseph Melenhorst, Simon F Lacey, John Scholler, Brian Keith, Regina M Young, Carl H June
Successful tumor eradication by chimeric antigen receptor-expressing (CAR-expressing) T lymphocytes depends on CAR T cell persistence and effector function. We hypothesized that CD4+ and CD8+ T cells may exhibit distinct persistence and effector phenotypes, depending on the identity of specific intracellular signaling domains (ICDs) used to generate the CAR. First, we demonstrate that the ICOS ICD dramatically enhanced the in vivo persistence of CAR-expressing CD4+ T cells that, in turn, increased the persistence of CD8+ T cells expressing either CD28- or 4-1BB-based CARs...
January 11, 2018: JCI Insight
Stephen J Schuster, Jakub Svoboda, Elise A Chong, Sunita D Nasta, Anthony R Mato, Özlem Anak, Jennifer L Brogdon, Iulian Pruteanu-Malinici, Vijay Bhoj, Daniel Landsburg, Mariusz Wasik, Bruce L Levine, Simon F Lacey, Jan J Melenhorst, David L Porter, Carl H June
BACKGROUND: Patients with diffuse large B-cell lymphoma or follicular lymphoma that is refractory to or that relapses after immunochemotherapy and transplantation have a poor prognosis. High response rates have been reported with the use of T cells modified by chimeric antigen receptor (CAR) that target CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited. METHODS: We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments...
December 28, 2017: New England Journal of Medicine
Stefanie R Bailey, Michelle H Nelson, Kinga Majchrzak, Jacob S Bowers, Megan M Wyatt, Aubrey S Smith, Lillian R Neal, Keisuke Shirai, Carmine Carpenito, Carl H June, Michael J Zilliox, Chrystal M Paulos
CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer...
December 6, 2017: Nature Communications
Katherine T Marcucci, Julie K Jadlowsky, Wei-Ting Hwang, Megan Suhoski-Davis, Vanessa E Gonzalez, Irina Kulikovskaya, Minnal Gupta, Simon F Lacey, Gabriela Plesa, Anne Chew, J Joseph Melenhorst, Bruce L Levine, Carl H June
Replication-competent retrovirus/lentivirus (RCR/L) and insertional oncogenesis are potential safety risks with integrating viruses in gene-modified cell therapies. As such, the Food and Drug Administration guidances outline RCR/L-monitoring methods throughout the entire gene therapy treatment cycle. We present data for 17 vector lots, 375 manufactured T cell products, and 308 patients post-infusion across both HIV and oncology indications, showing no evidence of RCR/L. Given our data, a Poisson probability model estimates that a single patient, or a group of patients, would need to be followed for at least 52...
January 3, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Denis Migliorini, Pierre-Yves Dietrich, Roger Stupp, Gerald P Linette, Avery D Posey, Carl H June
Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, an immunosuppressive microenvironment, and a partially permissive anatomic blood-brain barrier...
November 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Julia Tchou, Yangbing Zhao, Bruce L Levine, Paul J Zhang, Megan M Davis, Jan Joseph Melenhorst, Irina Kulikovskaya, Andrea L Brennan, Xiaojun Liu, Simon F Lacey, Avery D Posey, Austin D Williams, Alycia So, Jose R Conejo-Garcia, Gabriela Plesa, Regina M Young, Shannon McGettigan, Jean Campbell, Robert H Pierce, Jennifer M Matro, Angela M DeMichele, Amy S Clark, Laurence J Cooper, Lynn M Schuchter, Robert H Vonderheide, Carl H June
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602)...
December 2017: Cancer Immunology Research
Amrom E Obstfeld, Noelle V Frey, Keith Mansfield, Simon F Lacey, Carl H June, David L Porter, Jan J Melenhorst, Mariusz A Wasik
No abstract text is available yet for this article.
December 7, 2017: Blood
Nathan Singh, Junwei Shi, Carl H June, Marco Ruella
PURPOSE OF REVIEW: In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy. RECENT FINDINGS: Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies...
December 2017: Current Hematologic Malignancy Reports
Mohamed Abou-El-Enein, Toni Cathomen, Zoltán Ivics, Carl H June, Matthias Renner, Christian K Schneider, Gerhard Bauer
As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues.
October 5, 2017: Cell Stem Cell
Kenneth Cornetta, Lisa Duffy, Cameron J Turtle, Michael Jensen, Stephen Forman, Gwendolyn Binder-Scholl, Terry Fry, Anne Chew, David G Maloney, Carl H June
Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection...
September 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Biliang Hu, Jiangtao Ren, Yanping Luo, Brian Keith, Regina M Young, John Scholler, Yangbing Zhao, Carl H June
The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model...
September 26, 2017: Cell Reports
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
November 23, 2017: Blood
Carl H June, Jeremy T Warshauer, Jeffrey A Bluestone
No abstract text is available yet for this article.
August 4, 2017: Nature Medicine
David H Barlow, Todd J Farchione, Jacqueline R Bullis, Matthew W Gallagher, Heather Murray-Latin, Shannon Sauer-Zavala, Kate H Bentley, Johanna Thompson-Hollands, Laren R Conklin, James F Boswell, Amantia Ametaj, Jenna R Carl, Hannah T Boettcher, Clair Cassiello-Robbins
Importance: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. Objective: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders...
September 1, 2017: JAMA Psychiatry
Saad S Kenderian, Carl H June, Saar Gill
Adoptive transfer of genetically engineered T cells can lead to profound and durable responses in patients with hematologic malignancies, generating enormous enthusiasm among scientists, clinicians, patients, and biotechnology companies. The success of adoptive cellular immunotherapy depends upon the ability to manufacture good quality T cells. We discuss here the methodologies and reagents that are used to generate T cells for the preclinical study of chimeric antigen receptor T cell therapy for acute myeloid leukemia (AML)...
2017: Methods in Molecular Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"