Engineering CAR-T cells.
TLDR
The structure and evolution of chimeric antigen receptors are discussed, and the tools used for production of CAR-T cells are reported on, to address the challenges posed by the technology.Abstract:
Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated in other hematologic malignancies and solid tumors. CAR-T cells are generated by the T cells from patients’ or donors’ blood. After the T cells are expanded and genetically modified, they are reinfused into the patients. However, many challenges still need to be resolved in order for this technology to gain widespread adoption. In this review, we first discuss the structure and evolution of chimeric antigen receptors. We then report on the tools used for production of CAR-T cells. Finally, we address the challenges posed by CAR-T cells.read more
Citations
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Engineered T Cell Therapy for Cancer in the Clinic
Lijun Zhao,Yu Cao +1 more
TL;DR: It is predicted that genetically engineered T cell immunotherapies will become safe, well-tolerated, and effective therapeutics and bring hope to cancer patients.
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Targeting the IDO1 pathway in cancer: from bench to bedside.
Ming Liu,Ming Liu,Xu Wang,Lei Wang,Lei Wang,Xiaodong Ma,Zhaojian Gong,Zhaojian Gong,Shanshan Zhang,Shanshan Zhang,Yong Li +10 more
TL;DR: This review highlights recent preclinical and clinical progress in targeting the IDO1 pathway in cancer therapeutics, including peptide vaccines, expression inhibitors, enzymatic inhibitors, and effector inhibitors.
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Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
TL;DR: The successes and limitations of CAR T cell therapy are brought forth and the current understanding of how CAR T cells are designed to function, survive, and ultimately mediate their anti-tumoral effects are explored.
Journal ArticleDOI
CAR T cells in solid tumors: challenges and opportunities
Faroogh Marofi,Roza Motavalli,Vladimir Safonov,Lakshmi Thangavelu,Alexei Valerievich Yumashev,Markov Alexander,Navid Shomali,Max Stanley Chartrand,Yashwant Pathak,Mostafa Jarahian,Sepideh Izadi,Ali Hassanzadeh,Naghmeh Shirafkan,Safa Tahmasebi,Farhad Motavalli Khiavi +14 more
TL;DR: In this paper, the authors discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.
Journal ArticleDOI
A guide to manufacturing CAR T cell therapies
TL;DR: Current production processes being used for CAR T cells are detailed with a particular focus on efficacy, reproducibility, manufacturing costs and release testing, to quantify recent trends and track the uptake of new process technology.
References
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Journal ArticleDOI
Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia
TL;DR: A low dose of autologous chimeric antigen receptor-modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission.
Journal ArticleDOI
A Third-Generation Lentivirus Vector with a Conditional Packaging System
Tom Dull,Romain Zufferey,Michael C. Kelly,Ronald J. Mandel,Matthew Nguyen,Didier Trono,Luigi Naldini +6 more
TL;DR: It is demonstrated that the requirement for the tat gene can be offset by placing constitutive promoters upstream of the vector transcript, and the improved design presented here should facilitate testing of lentivirus vectors.
Journal ArticleDOI
Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2
Richard A. Morgan,James Chih-Hsin Yang,Mio Kitano,Mark E. Dudley,Carolyn M. Laurencot,Steven A. Rosenberg +5 more
TL;DR: It is speculated that the large number of administered cells localized to the lung immediately following infusion and were triggered to release cytokine by the recognition of low levels of ERBB2 on lung epithelial cells, consistent with a cytokine storm.
Journal ArticleDOI
Current concepts in the diagnosis and management of cytokine release syndrome
Daniel W. Lee,Rebecca Gardner,David L. Porter,Chrystal U. Louis,Nabil Ahmed,Michael C. Jensen,Stephan A. Grupp,Stephan A. Grupp,Crystal L. Mackall +8 more
TL;DR: A novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of C RS based on severity is presented, to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of the syndrome.
Journal ArticleDOI
Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia
David L. Porter,Wei-Ting Hwang,Noelle V. Frey,Simon F. Lacey,Pamela A. Shaw,Alison W. Loren,Adam Bagg,Katherine T. Marcucci,Angela Shen,Vanessa E. Gonzalez,David E Ambrose,Stephan A. Grupp,Anne Chew,Zhaohui Zheng,Michael C. Milone,Bruce L. Levine,J. Joseph Melenhorst,Carl H. June +17 more
TL;DR: The in vivo expansion of theCAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR, suggesting that disease eradication may be possible in some patients with advanced CLL.
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