Nejvíce citovaný článek - PubMed ID 25894527
A mass spectrometric-derived cell surface protein atlas
T-cell engagers represent a transformative approach to cancer immunotherapy leveraging bispecific and multispecific antibody constructs to redirect T-cell cytotoxicity toward malignant cells. These molecules bridge T cells and tumor cells by simultaneously binding CD3 on T cells and tumor-associated antigens on cancer cells, thereby enabling precise immune targeting even in immunologically "cold" tumors. Recent advancements include conditional T-cell engagers activated by tumor microenvironment proteases to minimize off-tumor toxicity as well as T-cell receptor-based engagers targeting intracellular antigens via MHC presentation. Clinical successes, such as Kimmtrak in metastatic uveal melanoma, underscore good potential of these modalities, while challenges persist in the management of cytokine release syndrome, neurotoxicity, and tumor resistance. Emerging multispecific engagers are aimed at enhancing efficacy via incorporation of costimulatory signals, thus offering a promising trajectory for next-generation immunotherapies. T-cell engagers are also gaining attention in the treatment of autoimmune disorders, where they can be designed to selectively modulate pathogenic immune responses. By targeting autoreactive T or B cells, T-cell engagers hold promise for restoring immune tolerance in such conditions as HLA-B*27-associated autoimmunity subtypes, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Engineering strategies that incorporate inhibitory receptors or tissue-specific antigens may further refine T-cell engagers' therapeutic potential in autoimmunity, by minimizing systemic immunosuppression while preserving immune homeostasis.
- Klíčová slova
- T-cell engager, autoimmunity, gene engineering, immunotherapy, soluble TCR,
- MeSH
- imunoterapie * metody MeSH
- lidé MeSH
- nádorové mikroprostředí imunologie MeSH
- nádory * imunologie terapie MeSH
- protilátky bispecifické terapeutické užití imunologie MeSH
- receptory antigenů T-buněk imunologie metabolismus MeSH
- T-lymfocyty * imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- protilátky bispecifické MeSH
- receptory antigenů T-buněk MeSH
CD molecules are surface molecules expressed on cells of the immune system that play key roles in immune cell-cell communication and sensing the microenvironment. These molecules are essential markers for the identification and isolation of leukocytes and lymphocyte subsets. Here, we present the results of the first phase of the CD Maps study, mapping the expression of CD1-CD100 (n = 110) on 47 immune cell subsets from blood, thymus, and tonsil using an eight-color standardized EuroFlow approach and quantification of expression. The resulting dataset included median antibody binding capacities (ABCs) and percentage of positivity for all markers on all subsets and was developed into an interactive CD Maps web resource. Using the resource, we examined differentially expressed proteins between granulocyte, monocyte, and dendritic cell subsets, and profiled dynamic expression of markers during thymocyte differentiation, T-cell maturation, and between functionally distinct B-cell subset clusters. The CD Maps resource will serve as a benchmark of antibody reactivities ensuring improved reproducibility of flow cytometry-based research. Moreover, it will provide a full picture of the surfaceome of human immune cells and serves as a useful platform to increase our understanding of leukocyte biology, as well as to facilitate the identification of new biomarkers and therapeutic targets of immunological and hematological diseases.
- Klíčová slova
- B-cell, CD marker, T-cell, expression profiling, flow cytometry, lymphocyte, monocyte, surfaceome,
- MeSH
- B-lymfocyty imunologie metabolismus MeSH
- CD antigeny biosyntéza MeSH
- datové soubory jako téma MeSH
- dendritické buňky imunologie metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- granulocyty imunologie metabolismus MeSH
- imunofenotypizace MeSH
- internet MeSH
- leukocyty imunologie metabolismus MeSH
- lidé MeSH
- lymfopoéza MeSH
- monocyty imunologie metabolismus MeSH
- peptidové mapování MeSH
- podskupiny lymfocytů imunologie metabolismus MeSH
- předškolní dítě MeSH
- průtoková cytometrie MeSH
- reprodukovatelnost výsledků MeSH
- separace buněk MeSH
- T-lymfocyty imunologie metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CD antigeny MeSH