Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells
TLDR
Co-transduced T cells destroy tumors that express both antigens but do not affect tumors expressing either antigen alone, and this 'tumor-sensing' strategy may help broaden the applicability and avoid some of the side effects of targeted T-cell therapies.Abstract:
To increase the tumor specificity of engineered T cells, Kloss et al. design an approach that relies on T cell recognition of two, rather than one, antigens.read more
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Journal ArticleDOI
CAR T cell immunotherapy for human cancer
TL;DR: Opportunities and challenges for entering mainstream oncology that presently face the CAR T field are described, with a focus on the challenges that have emerged over the past several years.
Journal ArticleDOI
The Basic Principles of Chimeric Antigen Receptor Design
TL;DR: This review focuses on the design ofCARs, including the requirements for optimal antigen recognition and different modalities to provide costimulatory support to targeted T cells, which include the use of second- and third generation CARs, costimulation ligands, chimericcostimulatory receptors, and cytokines.
Journal ArticleDOI
The Principles of Engineering Immune Cells to Treat Cancer
Wendell A. Lim,Carl H. June +1 more
TL;DR: This work discusses how synthetic biology approaches for cellular engineering is providing a broadly expanded set of tools for programming immune cells and how these tools could be used to design the next generation of smart T cell precision therapeutics.
Journal ArticleDOI
Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits.
Kole T. Roybal,Kole T. Roybal,Levi J. Rupp,Levi J. Rupp,Leonardo Morsut,Leonardo Morsut,Whitney J. Walker,Whitney J. Walker,Krista A. McNally,Krista A. McNally,Jason Park,Jason Park,Wendell A. Lim,Wendell A. Lim +13 more
TL;DR: A combinatorially activated T cell circuit in which a synthetic Notch receptor for one antigen induces the expression of a CAR for a second antigen opens the door to immune recognition of a wider range of tumors.
Journal ArticleDOI
Senescent cells: an emerging target for diseases of ageing.
Bennett G. Childs,Martina Gluscevic,Darren J. Baker,Remi-Martin Laberge,Dan Marquess,Jamie Dananberg,Jan M. van Deursen +6 more
TL;DR: Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.
References
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Journal ArticleDOI
T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia
Michael Kalos,Bruce L. Levine,David L. Porter,Sharyn I. Katz,Stephan A. Grupp,Stephan A. Grupp,Adam Bagg,Carl H. June +7 more
TL;DR: It is reported that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor ζ chain have potent non–cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL).
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
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
Paul F. Robbins,Richard A. Morgan,Steven A. Feldman,James Chih-Hsin Yang,Richard M. Sherry,Mark E. Dudley,John R. Wunderlich,Azam V. Nahvi,Lee J. Helman,Crystal L. Mackall,Udai S. Kammula,Michael S. Hughes,Nicholas P. Restifo,Mark Raffeld,Chyi-Chia Richard Lee,Catherine Levy,Yong F. Li,Mona El-Gamil,Susan L. Schwarz,Carolyn M. Laurencot,Steven A. Rosenberg +20 more
TL;DR: These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma.
Journal ArticleDOI
Tnf/tnfr family members in costimulation of t cell responses
TL;DR: This review focuses on CD27, 4-1BB, OX40, HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells, and shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
Journal Article
Prostate-specific membrane antigen expression in normal and malignant human tissues.
TL;DR: The decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation and the neoexpression of PSMA in endothelial cells of capillary beds in certain tumors may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.
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