ArticleProceedings of the National Academy of Sciences of the United States of America2023
Long-term persistence and functionality of adoptively transferred antigen-specific T cells with genetically ablated PD-1 expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Arming oncolytic herpes simplex virus with CXCL-11, IL-12 and a single-chain antibody against PD-1 to enhance CAR-T cell therapy in pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.Science immunology · 2026Article
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.Current gene therapy · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Special Issue "The Promising Future of CAR-Based Therapies: A Matter of Molecular Details".International journal of molecular sciences · 2025Article
- Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.Cancer science · 2025Article
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Revolutionising cancer intervention: the repercussions of CAR-T cell therapy on modern oncology practices.Medical oncology (Northwood, London, England) · 2025Review
- Alginate-based artificial antigen presenting cells expand functional CD8Biomaterials · 2025Article
- A bibliometric and knowledge-map study on the treatment of hematological malignancies with CAR-T cells from 2012 to 2023.Human vaccines & immunotherapeutics · 2024Article
- CRISPR/Cas9 Technology Providing the Therapeutic Landscape of Metastatic Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products.Blood advances · 2024Article
- CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.Nature communications · 2024Article
- Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors.Medical oncology (Northwood, London, England) · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Engagement of the inhibitory T cell receptor programmed cell death protein 1 (PD-1) associates with dysfunctional states of pathogen- or tumor-specific T cells. Accordingly, systemic antibody-mediated blockade of PD-1 has become a central target for immunotherapies but is also associated with severe toxicities due to loss of peripheral tolerance. Therefore, selective ablation of PD-1 expression on adoptively transferred T cells through direct genetic knockout (KO) is currently being explored as an alternative therapeutic approach. However, since PD-1 might also be required for the regulation of physiological T cell function and differentiation, the suitability of PD-1 as an engineering target is controversial. In this study, we systematically investigated the maintenance of T cell functionality after CRISPR/Cas9-mediated PD-1 KO in vivo during and after acute and chronic antigen encounter. Under all tested conditions, PD-1 ablation preserved the persistence, differentiation, and memory formation of adoptively transferred receptor transgenic T cells. Functional PD-1 KO T cells expressing chimeric antigen receptors (CARs) targeting CD19 could be robustly detected for over 390 d in a syngeneic immunocompetent mouse model, in which constant antigen exposure was provided by continuous B cell renewal, representing the longest in vivo follow-up of CAR-T cells described to date. PD-1 KO CAR-T cells showed no evidence for malignant transformation during the entire observation period. Our data demonstrate that genetic ablation of PD-1 does not impair functionality and longevity of adoptively transferred T cells per se and therefore may be pursued more generally in engineered T cell-based immunotherapy to overcome a central immunosuppressive axis.
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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.