Switching circuits: Modulating NK cell response to TGF-β using novel receptors
Turk, R.; Guo, L.; Belmont, B. J.; Bogard, N.; Chen, A. T.; Williams, M. D.; Young, M.; Stone, M. R.; Daines, B.; Darnell, M.
Show abstract
Engineered natural killer (NK) cells offer a promising treatment strategy for multiple therapeutic areas, yet tuning cell function to diverse environmental and inhibitory contexts remains a significant challenge. An attractive strategy for functional rescue in the presence of inhibitory ligands is the use of switch receptors, surface-expressed chimeric receptors that convert an external inhibitory cue into an intracellular activation signal. Here, we discover novel engineered switch receptors in NK cells that are responsive to TGF-{beta}, a soluble inhibitory factor present in many therapeutic contexts. Through a pooled screen of an 11,131 member library, we identified multiple novel signaling endodomains and endodomain combinations that improve both the acute cytotoxicity and persistence of NK cells in the presence of TGF-{beta}, demonstrating a novel and flexible approach to switch receptor discovery.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- NF-kB c-Rel is dispensable for the development but is required for the cytotoxic function of NK cells 94%
- A framework to identify antigen-expanded T Cell Receptor (TCR) clusters within complex repertoires 94%
- Naive and in vitro-activated primary mouse CD8+ T cells retain in vivo immune responsiveness after electroporation-based CRISPR/Cas9 genetic engineering 93%
Similar papers in this journal
- A Novel Cell Therapy for COVID-19 and Potential Future Pandemics: Virus Induced Lymphocytes (VIL) 94%
- Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals 93%
- Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications in a common base culture media system 92%
Similar papers in this journal
- Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy 93%
- A Spatiotemporal Map of Co-Receptor Signaling Networks Underlying B Cell Activation 93%
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 92%
Similar papers in this journal
- Engineered natural killer cells impede the immunometabolic CD73-adenosine axis in solid tumors 94%
- Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance 94%
- Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy 93%
Similar papers in this journal
- Precision Enhancement of CAR-NK Cells through Non-Viral Engineering and Highly Multiplexed Base Editing 95%
- Targeting CISH enhances natural cytotoxicity receptor signaling and reduces NK cell exhaustion to improve solid tumor immunity 94%
- Pooled screening for CAR function identifies novel IL13Rα2-targeted CARs for treatment of glioblastoma 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.