Phase I trial: Exosomes and mouse NK cell responses in vivo

In our lab, data was obtained from a phase I trial using peptide-pulsed Dex. Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell -dependent tumor rejection.
In this Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex onto NK cells, Dex promoting a IL-15Ra-dependent NK cell proliferation and a NKG2D-dependent activation resulting in an anti-metastatic effect. In humans, Dex bear functional IL-15R? which allow proliferation and IFNg secretion by NK cells. In contrast to immature DC, human Dex harbor NKG2D ligands on their surface leading to a direct engagement of NKG2D and NK cell activation ex vivo. In our phase I clinical trial, we highlight the capacity of Dex based-vaccines to restore the number and NKG2D-dependent function of NK cells in 7/14 patients. In conclusion, these data provide a mechanistic explanation on how Dex may stimulate non MHC restricted-anti-tumor effectors. Therefore, NK cell activation represents a new bioactivity for Dex leading to tumor recognition and regression in vivo.

• molecule type
• NKG2D,
• CD134,
• Major histocompatibility complex,
• Interferon gamma,
• CD4

• cell type
• T cell,
• dendritic cell,
• natural killer cell,
• autologous natural killer cell

• cell line type
• K562 cell line

• cell component type
• membrane,
• extracellular vesicular exosome

• organism type
• Mus musculus,
• Homo sapiens

• experimental design type
• cellular modification design experiment,
• in vivo design experiment

created over 16 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]