Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy.
Rebecca Gardner,Francesco Ceppi,Julie Rivers,Colleen Annesley,Corinne Summers,Agne Taraseviciute,Juliane Gust,Juliane Gust,Kasey J. Leger,Katherine Tarlock,Todd M. Cooper,Olivia Finney,Hannah Brakke,Daniel H. Li,Julie R. Park,Michael C. Jensen +15 more
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TLDR
The contention that early intervention with the use of tocilizumab and/or corticosteroids in subjects with early signs of CRS is without negative impact on anti-tumor potency of CD19CAR T cells is supported.About:
This article is published in Blood.The article was published on 2019-12-12 and is currently open access. It has received 171 citations till now. The article focuses on the topics: Cytokine release syndrome & Tocilizumab.read more
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T cell-engaging therapies - BiTEs and beyond.
TL;DR: The authors review the clinical results obtained with bispecific antibodies to date and discuss the challenges associated with this therapeutic approach and the proposed solutions aimed at preventing or minimizing toxicities, countering immune escape and broadening the indications for these treatments.
Journal ArticleDOI
Pediatric acute lymphoblastic leukemia.
TL;DR: This review describes key advances in the understanding of the biology of ALL and optimal approaches to risk-stratification and therapy, and it suggests key areas for basic and clinical research.
Journal ArticleDOI
Side-effect management of chimeric antigen receptor (CAR) T-cell therapy.
Maria-Luisa Schubert,Michael Schmitt,Lei Wang,C.A. Ramos,Karin Jordan,Carsten Müller-Tidow,Peter Dreger +6 more
TL;DR: This review summarizes the current understanding of CAR T-cell toxicity and its management and concludes that optimal management strategies of side-effects associated with CART-cell therapy are of high relevance.
Journal ArticleDOI
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL.
Nirali N. Shah,Daniel W. Lee,Bonnie Yates,Constance M. Yuan,Haneen Shalabi,Staci Martin,Pamela L. Wolters,Seth M. Steinberg,Eva H. Baker,Cindy Delbrook,Maryalice Stetler-Stevenson,Terry J. Fry,David F. Stroncek,Crystal L. Mackall +13 more
TL;DR: PURPOSECD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL) but relapse rates are high as discussed by the authors.
Journal ArticleDOI
Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity.
Olli Dufva,Jan Koski,Pilvi Maliniemi,Aleksandr Ianevski,Aleksandr Ianevski,Jay Klievink,Judith Leitner,Petri Pölönen,Helena Hohtari,Khalid Saeed,Tiina Hannunen,Pekka Ellonen,Peter Steinberger,Matti Kankainen,Tero Aittokallio,Tero Aittokallio,Tero Aittokallio,Mikko Antti Ilmari Keränen,Matti Korhonen,Satu Mustjoki +19 more
TL;DR: The results implicate death receptor signaling as an important mediator of cancer cell sensitivity to CAR T cell cytotoxicity, with potential for pharmacological targeting to enhance cancer immunotherapy.
References
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Journal ArticleDOI
Chimeric antigen receptor T cells for sustained remissions in leukemia.
Shannon L. Maude,Noelle Frey,Pamela A. Shaw,Richard Aplenc,David M. Barrett,Nancy Bunin,Anne Chew,Vanessa E. Gonzalez,Zhaohui Zheng,Simon F. Lacey,Yolanda D. Mahnke,J. Joseph Melenhorst,Susan R. Rheingold,Angela Shen,David T. Teachey,Bruce L. Levine,Carl H. June,David L. Porter,Stephan A. Grupp +18 more
TL;DR: Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL and was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed.
Journal ArticleDOI
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
Sattva S. Neelapu,Frederick L. Locke,Nancy L. Bartlett,Lazaros J. Lekakis,David B. Miklos,Caron A. Jacobson,Ira Braunschweig,Olalekan O. Oluwole,Tanya Siddiqi,Yi Lin,John M. Timmerman,Patrick J. Stiff,Jonathan W. Friedberg,Ian W. Flinn,Andre Goy,Brian T. Hill,Mitchell R. Smith,Abhinav Deol,Umar Farooq,Peter A. McSweeney,Javier Munoz,Irit Avivi,Januario E. Castro,Jason R. Westin,Julio C. Chavez,Armin Ghobadi,Krishna V. Komanduri,Ronald Levy,Eric D. Jacobsen,Thomas E. Witzig,Patrick M. Reagan,Adrian Bot,John J. Rossi,Lynn Navale,Yizhou Jiang,Jeff Aycock,Meg Elias,David Z. Chang,Jeff Wiezorek,William Y. Go +39 more
TL;DR: Patients with refractory large B‐cell lymphoma who received CAR T‐cell therapy with axi‐cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events.
Journal ArticleDOI
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Shannon L. Maude,Theodore W. Laetsch,Jochen Buechner,S. Rives,Michael Boyer,Henrique Bittencourt,Peter Bader,Michael R. Verneris,Heather E. Stefanski,G.D. Myers,Muna Qayed,B. De Moerloose,Hidefumi Hiramatsu,Krysta Schlis,Kara L. Davis,Paul L. Martin,Eneida R. Nemecek,Gregory A. Yanik,Christina Peters,André Baruchel,Nicolas Boissel,Francoise Mechinaud,Adriana Balduzzi,Joerg Krueger,Carl H. June,Bruce L. Levine,Patricia A. Wood,Tanya Taran,Mimi Leung,Karen Thudium Mueller,Yiyun Zhang,Kapildeb Sen,David Lebwohl,Michael A. Pulsipher,Stephan A. Grupp +34 more
TL;DR: In this global study of CAR T‐cell therapy, a single infusion of tisagenlecleucel provided durable remission with long‐term persistence in pediatric and young adult patients with relapsed or refractory B‐cell ALL, with transient high‐grade toxic effects.
Journal ArticleDOI
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.
Stephan A. Grupp,Michael Kalos,David M. Barrett,Richard Aplenc,David L. Porter,Susan R. Rheingold,David T. Teachey,Anne Chew,Bernd Hauck,J. Fraser Wright,Michael C. Milone,Bruce L. Levine,Carl H. June +12 more
TL;DR: The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL.
Journal ArticleDOI
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Daniel W. Lee,James N. Kochenderfer,Maryalice Stetler-Stevenson,Yongzhi K Cui,Cindy Delbrook,Steven A. Feldman,Terry J. Fry,Rimas J. Orentas,Marianna Sabatino,Nirali N. Shah,Seth M. Steinberg,Dave Stroncek,Nick Tschernia,Constance M. Yuan,Hua Zhang,Ling Zhang,Steven A. Rosenberg,Alan S. Wayne,Crystal L. Mackall +18 more
TL;DR: CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
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