Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors

Autor: Wendell A. Lim, Levi J. Rupp, Krista A. McNally, Choe Joseph H, Kole T. Roybal, Whitney J. Walker, Leonardo Morsut, Isabel Kolinko, Jasper Z. Williams
Rok vydání: 2016
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
T-Lymphocytes
Cytotoxicity
medicine.medical_treatment
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Immunotherapy
Adoptive
Medical and Health Sciences
TNF-Related Apoptosis-Inducing Ligand
Immunologic
Neoplasms
Receptors
Tumor Microenvironment
Receptor
Cell Engineering
Tumor
Biological Sciences
3. Good health
Cell biology
Artificial
Cytokines
CARs
immunotherapy
Development of treatments and therapeutic interventions
Antibody
Transcription
Biotechnology
Notch
Receptors
Antigen
T-Cell
T cells
Bioengineering
Biology
cellular engineering
Article
Antibodies
General Biochemistry
Genetics and Molecular Biology
Cell Line
synthetic Notch
Vaccine Related
03 medical and health sciences
Immune system
Genetic
Antigen
medicine
Humans
cancer
Tumor microenvironment
5.2 Cellular and gene therapies
Inflammatory and immune system
Immunotherapy
Th1 Cells
030104 developmental biology
T cell differentiation
biology.protein
Cytokine secretion
synthetic biology
Developmental Biology
Zdroj: Cell, vol 167, iss 2
ISSN: 0092-8674
DOI: 10.1016/j.cell.2016.09.011
Popis: Redirecting Tcells to attack cancer using engineered chimeric receptors provides powerful new therapeutic capabilities. However, the effectiveness of therapeutic Tcells is constrained by the endogenous Tcell response: certain facets of natural response programs can be toxic, whereas other responses, such as the ability to overcome tumor immunosuppression, are absent. Thus, the efficacy and safety of therapeutic cells could be improved if we could custom sculpt immune cell responses. Synthetic Notch (synNotch) receptors induce transcriptional activation in response to recognition of user-specified antigens. We show that synNotch receptors can be used to sculpt custom response programs in primary Tcells: they can drive a la carte cytokine secretion profiles, biased Tcell differentiation, and local delivery of non-native therapeutic payloads, such as antibodies, in response to antigen. SynNotch Tcells can thus be used as a general platform to recognize and remodel local microenvironments associated with diverse diseases.
Databáze: OpenAIRE
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