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Articles by Leon Su
Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics
Editor’s summary Structured Abstract Abstract Supplementary Materials References and Notes Information & Authors Metrics & Citations Check Access References Figures Tables Media Share Editor’s summary Cytokines are molecular messengers that modulate immune responses. Rodriguez et al. designed hybrid cytokines called Trikines that mediate intracellular signaling from the cell surface by assembling three-chain cytokine receptor complexes.
IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy
Keywords adoptive T cell therapy JAK/STAT common gamma chain IL-9 IL-9R cancer immunotherapy cytokines cell signaling CAR T cell therapy TCR T cell therapy Introduction Common γ-chain (γc) cytokines are critical regulators of T cell differentiation and function, exerting their effects through JAK/STAT signaling pathways.1 Their potential to enhance adoptive T cell therapy for cancer has long been recognized.2 Building on an orthogonal interleukin (IL)-2 system in which we swapped...
IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy
Protein production DNA encoding mouse and human IL-2 and IL-9, and mouse IL-9Q115T were cloned into the mammalian expression vector pD649, which includes a C-terminal 8xHis tag for affinity purification. DNA encoding mouse serum albumin (MSA) was purchased from Integrated DNA Technologies (IDT) and cloned into pD649 as an N-terminal fusion.
Expanding the cytokine receptor alphabet reprograms T cells into diverse states - Nature
Abstract T cells respond to cytokines through receptor dimers that have been selected over the course of evolution to activate canonical JAK–STAT signalling and gene expression programs1. However, the potential combinatorial diversity of JAK–STAT receptor pairings can be expanded by exploring the untapped biology of alternative non-natural pairings.
Redirecting immune signaling with cytokine adaptors - Nature Communications
Abstract Cytokines are signaling molecules that coordinate complex immune processes and are frequently dysregulated in disease. While cytokine blockade has become a common therapeutic modality, cytokine agonism has had limited utility due to the widespread expression of cytokine receptors with pleiotropic effects.
Stat5 opposes the transcription factor Tox and rewires exhausted CD8+ T cells toward durable effector-like states during chronic antigen exposure
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A structural blueprint for interleukin-21 signal modulation
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Facile repurposing of peptide–MHC-restricted antibodies for cancer immunotherapy - Nature Biotechnology
Abstract Monoclonal antibodies (Abs) that recognize major histocompatability complex (MHC)-presented tumor antigens in a manner similar to T cell receptors (TCRs) have great potential as cancer immunotherapeutics.
Publisher Correction: Potentiating adoptive cell therapy using synthetic IL-9 receptors - Nature
Correction to: Nature https://doi.org/10.1038/s41586-022-04801-2 Published online 8 June 2022 This paper was originally published under a standard Springer Nature license (© The Author(s), under exclusive licence to Springer Nature Limited). It is now available as an open-access paper under a Creative Commons Attribution 4.0 International license, © The Author(s). The error has been corrected in the HTML and PDF versions of the article.
Potentiating adoptive cell therapy using synthetic IL-9 receptors - Nature
Abstract Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning chemotherapy1,2.
The tissue protective functions of interleukin-22 can be decoupled from pro-inflammatory actions through structure-based design
Highlights • 2.6-Å-resolution structure of a stabilized IL-22 receptor ternary complex • Structure-based design of STAT3-biased IL-22 receptor agonists • Biased IL-22 variant 22-B3 elicits tissue-selective STAT3 activation in vivo • 22-B3 uncouples the tissue-protective and pro-inflammatory functions of IL-22 Summary Interleukin-22 (IL-22) acts on epithelial cells to promote tissue protection and regeneration, but can also elicit pro-inflammatory effects, contributing to disease pathology.
Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10
Cryo-EM helps engineer enhanced IL-10 Interleukin-10 (IL-10) binds to the IL-10 receptor (IL-10R), comprising two high-affinity α chains and two low-affinity β chains. Depending on the cellular context of its recognition, IL-10 can either suppress or activate immune responses. This pleiotropic behavior has complicated efforts to use IL-10 as an anti-inflammatory agent. Saxton et al.
Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells
Highlights • Crystal structure of the complete IL-23 receptor complex • Cryo-EM maps of the complete IL-12 and IL-23 receptor complexes • The p40 subunit of IL-12 and IL-23 is a common gateway for induction of STAT signaling • T-cell-biased IL-12 agonists elicit anti-tumor response without inducing toxicity Summary Interleukin-12 (IL-12) and IL-23 are heterodimeric cytokines that are produced by antigen-presenting cells to regulate the activation and differentiation of lymphocytes, and they...
Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells
Ardolino M. Azimi C.S. Iannello A. Trevino T.N. Horan L. Zhang L. Deng W. Ring A.M. Fischer S. Garcia K.C. Raulet D.H. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. J. Clin. Invest. 2014; 124: 4781-4794 Aste-Amezaga M. D’Andrea A. Kubin M. Trinchieri G. Cooperation of natural killer cell stimulatory factor/interleukin-12 with other stimuli in the induction of cytokines and cytotoxic cell-associated molecules in human T and NK cells. Cell. Immunol.
Immune receptor inhibition through enforced phosphatase recruitment
Abstract Antibodies that antagonize extracellular receptor–ligand interactions are used as therapeutic agents for many diseases to inhibit signalling by cell-surface receptors1. However, this approach does not directly prevent intracellular signalling, such as through tonic or sustained signalling after ligand engagement. Here we present an alternative approach for attenuating cell-surface receptor signalling, termed receptor inhibition by phosphatase recruitment (RIPR).
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