ArticleMolecular therapy. Methods & clinical development2017
Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway.
Article in Molecular therapy. Methods & clinical development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Immune Cytolytic Activity Correlates with Tumor Microenvironmental Aberrations in Colorectal Cancer.International journal of molecular sciences · 2026Article
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- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Effects of CMV on T and NK Cells; With Emphasis on Immunometabolism.BioMed research international · 2026Review
- Construction of an immune prediction model for osteosarcoma based on coagulation-related genes.Discover oncology · 2025Article
- Engineering anti-BCMA CAR T cells for enhancing myeloma killing efficacy via apoptosis regulation.Nature communications · 2025Article
- Mitochondrial priming in therapy-induced senescence: implications for CAR-T/NK immunosenolytic therapy.Frontiers in immunology · 2025Review
- Identification of Biomarkers Based on Starvation Response-Related Genes for Assessing the Immune Profile and Prognosis in Lung Adenocarcinoma.International journal of genomics · 2025Article
- Immune Cytolytic Activity and Strategies for Therapeutic Treatment.International journal of molecular sciences · 2024Review
- Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies.Cancer immunology research · 2023Article
- Analysis of scRNA-seq and bulk RNA-seq demonstrates the effects of EVI2B or CD361 on CD8Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer.Cancer medicine · 2021Article
- Molecular correlates of immune cytolytic subgroups in colorectal cancer by integrated genomics analysis.NAR cancer · 2021Article
- Article
- Cytolytic activity correlates with the mutational burden and deregulated expression of immune checkpoints in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer.Annals of surgical oncology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is great potential for engineering cellular therapeutics by repurposing biological systems. Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.
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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.