Engineering T cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors
By Kole T. Roybal, Jasper Z. Williams, Leonardo Morsut, Levi J. Rupp, Isabel Kolinko, Joseph H. Choe, Whitney J. Walker, Krista A. McNally, Wendell A. Lim. Cell, 2016
665 citations recorded by the source corpus.
Redirecting T cells to attack cancer using engineered chimeric receptors provides powerful new therapeutic capabilities. But the effectiveness of therapeutic T cells is constrained by the endogenous T cell 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 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 T cells: they can drive a la carte cytokine secretion profiles, biased T cell differentiation, and local delivery of non-native therapeutic payloads, such as antibodies, in response to antigen. SynNotch T cells can thus be used as a general platform to recognize and remodel local microenvironments associated with diverse diseases.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/5a5cd6bf1eaffefd77b04e82381979475fb5cff3
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Oncology
Citations in the corpus
- The Principles of Engineering Immune Cells to Treat Cancer (2017, background): “For example, the synNotch receptor system described earlier can be used to engineer T cells that produce specific secreted payloads in response to recognition of a target antigen (Roybal et al., 2016b).”