| Autor: |
Alexandra Foster, Shubhanchi Nigam, David S Tatum, Itay Raphael, Jide Xu, Rajeev Kumar, Elizabeth Plakseychuk, Joseph D Latoche, Sarah Vincze, Bo Li, Rajan Giri, Lauren H McCarl, Robert Edinger, Murat Ak, Vishal Peddagangireddy, Lesley M Foley, T Kevin Hitchens, Rivka R Colen, Ian F Pollack, Ashok Panigrahy, Darren Magda, Carolyn J Anderson, W Barry Edwards, Gary Kohanbash |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 71, Iss , Pp 103571- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2021.103571 |
| Popis: |
Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
