Clinical trials of cancer patients treated with exosomes

Our lab obtained data on the ability of NK cell IFN-gamma production to predict long term survival in advanced GISTs treated with IM.

Background: Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for imatinib mesylate (IM) (Gleevec®, Novartis), a specific inhibitor of these tyrosine kinase receptors. Predictive factors for the response to IM pertain to the intrinsic features of GIST tumor cells but not to the host. Besides its direct antiproliferative activity on tumor cells, IM can trigger NK cell effectors which contribute to tumor regression in mice.

Therefore, we addressed whether NK cell functions could be independent prognostic factors predicting long term survival to IM therapy.

Methods: The functional phenotype of NK cells was followed up in 77 GIST patients enrolled in two Phase III trials from 2 institutions testing dosing or duration of IM administration (EORTC 62005 and BFR14 trials). “Immunological responders” were defined as patients whose NK cell IFN-gamma values after 2 months of IM were higher or equal to the baseline value at entry in the trial. The prognostic impact of IFN-gamma on progression-free survival was assessed by a Wald test in a Cox regression analysis using the landmark method and stratified by trial and on the c-kit mutational status.

Results:
56 patients were evaluable for the NK cell IFN-gamma responses at baseline and 2 months. Their median follow-up for progression-free survival was 3.7 years. 34/56 patients were “immunological responders” to IM. In the Cox regression analysis stratified by trial, immunological responders possessed a hazard ratio of progression or death equal to 0.29 (95% CI [0.12-0.70], p=0.006) as compared to non-responders. Kaplan-Meier two-year survival estimates were 85% for immunological responders and 50% for non-responders. Moreover, the immunological response added prognostic value to the c-kit mutation.

Conclusion:
The NK cell IFN-gamma production after two months of treatment could be considered as an independent predictor of long term survival in advanced GISTs treated with IM.

• molecule type
• NKp30 gene,
• Molecular entity,
• NKG2D,
• Interleukin-2,
• Interleukin-12 cytokine,
• Interleukin-18,
• Interferon gamma

• cell type
• natural killer cell,
• mature dendritic cell,
• gastrointestinal stromal tumor cell

• cell component type
• extracellular vesicular exosome

• organism type
• Mus musculus,
• Homo sapiens

• bodily part type
• blood serum specimen

• experimental design type
• in vivo design experiment

created over 15 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]