ArticleThe Journal of clinical investigation2023
Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Genetic Engineering of Tumor-Infiltrating Lymphocytes (TIL) via a T-Editor Platform to Enhance Anti-Tumor Activity.Cancer science · 2026Article
- T cell receptor repertoire dynamics and newly identified functional regulators of autologous tumor-infiltrating lymphocyte therapy in advanced solid tumors.Journal of translational medicine · 2026Article
- Potent Cytotoxic Tumor-Infiltrating Lymphocytes Can Be Generated from Immune-Excluded Chondrosarcomas Using Regulatable Membrane-Bound IL15.Cancer immunology research · 2026Article
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- Advances in cell therapy for solid tumours: European perspective and future directions.The Lancet regional health. Europe · 2026Review
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- CISH, a key intracellular checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints.Communications biology · 2026Article
- CRISPR-screen informed engineered T cell therapies.Frontiers in immunology · 2026Review
- Evolving therapeutic pipeline for tumor-infiltrating lymphocytes in metastatic melanoma - a review.Frontiers in immunology · 2026Review
- Tumor reactivity assessment using clonal expression reveals tumor reactive CD8Frontiers in immunology · 2026Article
- Tumor-infiltrating lymphocyte expansion protocols for adoptive cell therapy in cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- Immunoregulatory Microenvironment in the Elderly Skin.JID innovations : skin science from molecules to population health · 2025Article
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- CRISPR/Cas9-mediated PD-1 attenuation enhances tumor infiltrating lymphocyte-based adoptive cellular therapy in humanized-PDX model of hepatocellular carcinoma.Translational oncology · 2025Article
- Highly efficient gene knockout in tumor-infiltrating lymphocytes by adenine base editing.Molecular therapy. Oncology · 2025Article
- A STUB1-CHIC2 complex inhibits CD8Nature immunology · 2025Article
- IL-2-independent expansion, persistence, and antitumor activity in TIL expressing regulatable membrane-bound IL-15.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
Corrections and comments
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Authors and funding
28 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine CD8+ T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cells (Texprog) in tumors. A comprehensive CRISPR tiling screen of the SOCS1-coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with an sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo antitumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.