BioProject

Adoptive cell therapies (ACT) with cytotoxic T-cell targeting melanocytic antigens can achieve remissions in metastatic melanoma patients, but tumours frequently relapse. More...

Adoptive cell therapies (ACT) with cytotoxic T-cell targeting melanocytic antigens can achieve remissions in metastatic melanoma patients, but tumours frequently relapse. To study the underlying mechanisms of resistance we have generated a genetically engineered mouse melanoma model that faithfully recapitulates tumour regression, remission and relapse as seen in patients. HCmel3 mouse melanoma cells were injected into syngneic C57/BL6 (H-2b) mice. We performed transcriptional profiling of control, relapsed and re-transplanted relapsed tumours to characterize the changes in gene expression patterns associated with the respective treament conditions. In addition, we analysed the transcription profile of ACT relapsed melanoma cultures in vitro and the transcriptional response to the inflammatory cytokine Tnf-alpha. The study aimed to identify molecular mechanisms contributing to ACT resistance to optimize therapeutic regimens in the clinic. Overall design: Total RNA obtained from five biological replicates (rep) of control, relapsed and re-transplanted HCmel3 mouse melanomas in vivo and two biological replicates (rep) of HCmel3 cells, HCmel3-R (relapse) cells and Tnf-alpha treated HCmel3 cells in vitro. Less...