ArticleInternational journal of molecular sciences2022
The Effects of Chimeric Antigen Receptor (CAR) Hinge Domain Post-Translational Modifications on CAR-T Cell Activity.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Efficacy analysis of CAR-T cells against CD123-positive malignant tumors and exploration of the feasibility of combination therapy with venetoclax.Annals of hematology · 2026Article
- Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk.International journal of molecular sciences · 2025Review
- Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy.Frontiers in immunology · 2025Review
- Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.Frontiers in oncology · 2025Review
- Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.Journal for immunotherapy of cancer · 2024Article
- Novel OX40 and 4-1BB derived spacers enhance CD30 CAR activity and safety in CD30 positive lymphoma models.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Targeted chemotherapy via HER2-based chimeric antigen receptor (CAR) engineered T-cell membrane coated polymeric nanoparticles.Bioactive materials · 2024Article
- CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.Frontiers in immunology · 2024Review
- Designing Chimeric Antigen Receptors for Myeloid Immune Cells.Journal of cancer biology & research · 2024Article
- Refining chimeric antigen receptors via barcoded protein domain combination pooled screening.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Complexities in comparing the impact of costimulatory domains on approved CD19 CAR functionality.Journal of translational medicine · 2023Review
- The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.International journal of molecular sciences · 2022Article
- Binding and Efficacy of Anti-Robo4 CAR-T Cells against Solid Tumors.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
To improve the efficacy and safety of chimeric antigen receptor (CAR)-expressing T cell therapeutics through enhanced CAR design, we analysed CAR structural factors that affect CAR-T cell function. We studied the effects of disulphide bonding at cysteine residues and glycosylation in the HD on CAR-T function. We used first-generation CAR[V/28/28/3z] and CAR[V/8a/8a/3z], consisting of a mouse vascular endothelial growth factor receptor 2 (VEGFR2)-specific single-chain variable fragment tandemly linked to CD28- or CD8α-derived HD, transmembrane domain (TMD) and a CD3ζ-derived signal transduction domain (STD). We constructed structural variants by substituting cysteine with alanine and asparagine (putative N-linked glycosylation sites) with aspartate. CAR[V/28/28/3z] and CAR[V/8a/8a/3z] formed homodimers, the former through a single HD cysteine residue and the latter through the more TMD-proximal of the two cysteine residues. The absence of disulphide bonds did not affect membrane CAR expression but reduced antigen-specific cytokine production and cytotoxic activity. CAR[V/28/28/3z] and CAR[V/8a/8a/3z] harboured one N-linked glycosylation site, and CAR[V/8a/8a/3z] underwent considerable O-linked glycosylation at an unknown site. Thus, N-linked glycosylation of CAR[V/28/28/3z] promotes stable membrane CAR expression, while having no effect on the expression or CAR-T cell activity of CAR[V/8a/8a/3z]. Our findings demonstrate that post-translational modifications of the CAR HD influence CAR-T cell activity, establishing a basis for future CAR design.
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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.