Dr Thielemans talks to ecancertv the 1st Immunotherapy of Cancer Conference ( ITOC ) in Munich.
Electroporation of dendritic cells (DC) with mRNA allows the loading of these cells with tumour antigens and the functional modification of a cellular vaccine.
To this goal, the team provided three different molecular adjuvants to immature, monocyte derived DCs through electroporation with mRNA coding for CD40L, CD70 and caTLR4 or so-called TriMix mRNA.
At Vrije Universiteit, Brussels, clinical trials in pretreated advanced melanoma patients are being performed.
These patients are treated with TriMixDC-MEL, a mixture of TriMix-DC co-electroporated with mRNA encoding a fusion of DC-LAMP and 4 different melanoma associated antigens (gp100, tyrosinase, MAGE-C2 or MAGE-A3).
In a pilot clinical trial, 24x106 TriMixDC-MEL cells were administrated solely by the intradermal (ID) route. Subsequently, a phase IB was conducted to investigate the safety of administrating TriMixDC-MEL by the intravenous (IV) and ID-route. ID administration of TriMixDC-MEL was found to be feasible, safe, effectively stimulating CD8 T-cell responses, but did not result in objective tumour responses.
In contrast, the combined ID/IV administration is associated with distinct but manageable side-effects and has seemingly superior clinical activity as compared to DC administered solely ID in patients with pretreated advanced melanoma.
The team investigated the safety and activity of TriMixDC-MEL combined with ipilimumab. This phase II study of TriMixDC-MEL ID/IV in combination with ipilimumab demonstrates anti-melanoma activity in over 50% of the patients with therapy resistant advanced melanoma.