Retraction Note: A homing system targets therapeutic T cells to brain cancer
| Autor: | Dai Fukumura, Matthew L. Baker, Fong Lam, Tiara T. Byrd, Maksim Mamonkin, Michael D. Taylor, Shahenda El-Naggar, Ankita Shree, Antonella Pignata, Nabil Ahmed, Malini Mukherjee, Fabio Stossi, Shanmugarajan Krishnan, Rakesh K. Jain, Sean P. Marrelli, Jordan S. Orange, Ahmed Z. Gad, Jun Ren, Vita S. Salsman, Kristen Fousek, Heba Samaha, Julien Dubrulle, Sujith K. Joseph, Meenakshi Hegde, Poul H. Sorensen, Sung-Ha Hong, Thomas Shum |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Multidisciplinary
Endothelium Chemistry Multiple sclerosis Activated-Leukocyte Cell Adhesion Molecule medicine.disease Extravasation Article 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation 030220 oncology & carcinogenesis medicine Cancer research Cytotoxic T cell 030217 neurology & neurosurgery ALCAM Homing (hematopoietic) |
| Zdroj: | Nature |
| Popis: | Successful T cell immunotherapy for brain cancer requires that the T cells can access tumour tissues, but this has been difficult to achieve. Here we show that, in contrast to inflammatory brain diseases such as multiple sclerosis, where endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro-inflammatory cells, cancer endothelium downregulates these molecules to evade immune recognition. By contrast, we found that cancer endothelium upregulates activated leukocyte cell adhesion molecule (ALCAM), which allowed us to overcome this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS). We re-engineered the natural ligand of ALCAM, CD6, in a manner that triggers initial anchorage of T cells to ALCAM and conditionally mediates a secondary wave of adhesion by sensitizing T cells to low-level ICAM1 on the cancer endothelium, thereby creating the adhesion forces necessary to capture T cells from the bloodstream. Cytotoxic HS T cells robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumour activity. We have therefore developed a molecule that targets the delivery of T cells to brain cancer. |
| Databáze: | OpenAIRE |
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