The ex vivo TriMix-DC product (autologous dendritic cells electroporated with TriMix and antigen mRNA) has been validated in mouse models, two phase I clinical studies and two phase IIa clinical studies in melanoma patients (as stand-alone and in combination with ipilimumab).
Studies in melanoma patients showed a significant increased 1-year survival, best overall response, disease control and progression free survival (ASCO 2014 / ECCO 2015). The data suggest that the complete response of the combination treatment (TriMixDC plus ipilimumab) increased by a factor 5 - 10 (> 20 %) in comparison to ipilimumab alone (2-4%).
The findings of the study with TriMixDC in combination with ipilimumab in melanoma patients were published in March 2016 in the Journal of Clinical Oncology, with the conclusion that "The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma."
Enhancing the T-cell stimulatory capacity of human dendritic cells by co-electroporation with CD40L, CD70 and constitutively active TLR4 ecoding mRNA
A Bonehill, S Tuyaerts, A Van Nuffel, C Heirman, K Fostier, B Neyns and Thielemans Mol Ther. 2008 Jun;16(6):1170-80
Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients
A Bonehill, V François, A Van Nuffel, DColau,J Corthals, P van der Bruggen, S Tuyaerts, B Neyns, C Heirman and Thieleman Clin Cancer Res. 2009 May 15;15(10):3366-75
Phase II study of autologous mRNA electroporated dendritic cells (TriMixDC-MEL) in combination with ipilimumab in patients with pretreated advanced melanoma
B Neyns, S Wilgenhof, J Corthals, C Heirman, K Thielemans Presentation at the 2014 ASCO Annual Meeting
Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy
S Van Lint, C Goyvaerts, S Maenhout, L Goethals, A Disy, D Benteyn, J Pen, A Bonehill, C Heirman, K Breckpot and K Thielemans Cancer Res. 2012 Apr 1;72(7):1661-71.
The ReNAissanCe of mRNAbased cancer therapy
S Van Lint, D Renmans, K Broos, H Dewitte, I Lentacker, C Heirman, K Breckpot and K Thielemans* Expert Rev Vaccines. 2015 Feb;14(2):235-51
Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in Ppatients with advanced melanoma
S Wilgenhof, A Van Nu?el, J Corthals, C Heirman, S Tuyaerts, D Benteyn, A De Coninck, I Van Riet, G Verfaillie, J Vandeloo, A Bonehill, K Thielemans, and B Neyns J Immunother. 2011 Jun;34(5):448-56.
A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients
S. Wilgenhof, A. M. T. Van Nuffel, D. Benteyn, J. Corthals, C. Aerts, C. Heirman, A. Bonehill, K. Thielemans, B. Neyns and I. Van Riet Ann Oncol. 2013 Oct;24(10):2686-93.