Dendritic cell vaccination combined with CTLA4 blockade

Bookmark and Share
Published: 25 Mar 2014
Views: 3644
Rating:
Save
Dr Kris Thielemans - Medical School of the VUB, Brussels, Belgium

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.