Research Updates & Results

Adoptive immunotherapy is showing promise in the clinical setting.  This approach involves depleting the immune system of the patient, then injecting specially engineered T-cells.  The T-cells cause apoptosis in tumor cells.  Some cells, however, are resistant to apoptosis; this is a limiting factor in this therapeutic approach.

Our hypothesis is that adoptive immunotherapy is limited by specific survival mechanisms acquired by the tumor target.  We further hypothesize that small molecure therapy can be used interfere with these survival mechanisms.

We will establish patient-derived melanoma lines and assess their in vitro sensitivity to engineered T cells.  For those cells that are resistant to apoptosis, we will then determine the presence of surface peptide-MHC complex, a frequent means by which tumor cell evade immune attack.

We will then evaluate whether modification of key apoptosis regulatory molecules and/or cell signaling pathways are implicated in resistance to immunotherapy and if so which gene product(s) is the main resistant factor.

Finally, we will assess the ability of a clinically approved histone deacetylase inhibitor (SAHA) to reverse the apoptosis-resistance phenotype of patient-derived melanoma cell lines.