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Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7547
- Publication Year :
- 2022
-
Abstract
- Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision.
- Subjects :
- Organic Chemistry
Galactosylceramides
General Medicine
Catalysis
invariant natural killer T (iNKT) cell
α-GalCer
cancer immunotherapy
solid tumor
melanoma
lung cancer
CD1d
bioluminescence live animal imaging (BLI)
Computer Science Applications
Inorganic Chemistry
Mice
Neoplasms
Animals
Humans
Natural Killer T-Cells
Tissue Distribution
Physical and Theoretical Chemistry
Antigens, CD1d
Molecular Biology
Spectroscopy
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....db97db13ef77003623bb9e703f53af2a