Publication date: 28/05/2019
Metastatic melanoma still has very poor prognosis in spite of the addition of checkpoint inhibitors. In a study performed at the birth of immunotherapies (study started 2011) the effects of dendritic cell mRNA vaccine together with a checkpoint inhibitor (ipilimumab) showed clinical efficacy in the TriMix DC-MEL IPI study. We now have long term follow up showing 7 out of 39 patients long term disease free. The objective of the present sub-study was to retrospectively analyse patient immune cell samples, to link disease free survival with immune response.
Immunotherapies, VUB, UZ Brussel and HistoGeneX researchers today presented new data from the TriMixDC-MEL IPI study at the CIMT Annual Meeting. The study was performed using dendritic cells electroporated with immunostimulatory mRNA against tumor associated antigens to elicit immune attack against the tumor.
In the sub-study a number of immune tests, including ELISPOT and intracellular cytokine staining (ICS), were performed on historic samples available from 15 patients focusing on cellular immune responses towards tumor associated antigens (TAAs) used in the eTheRNA dendritic cell vaccine (gp100, tyrosinase, MAGE A3, MAGE C2). Data show that many of the patients that showed disease cure had multi-antigen response and showed high numbers of CD8+ T-cells reacting towards these TAAs. Although the study is of limited size, it is likely that the patients who showed these multi-antigen, high CD8+ T-cell responses were the ones that were responded completely to the treatment and survived the metastatic melanoma.
We believe this is the first time immune responses elicited by dendritic cell mRNA vaccine combined with the checkpoint inhibitor ipilimumab have been shown to be superior in patients showing a complete treatment response.
Professor Bart Neyns VUB said “it is very encouraging that we see long-term disease-free patients in this study and that we can now start to correlate this with specific immune response. It is possible we can use these response data as a measure by which future treatments are assessed”
Professor Kris Thielemans of VUB and founder of eTheRNA Immunotherapies stated “obviously we had high hopes for this study when it was initiated and we now see the long-term effects. With eTheRNA we continue to innovate and we now have several new immunostimulatory therapies in the pipeline, based on the learnings from the TriMix-DC-MEL IPI study”
About eTheRNA immunotherapies
eTheRNA immunotherapies is a clinical-stage company delivering innovative cancer immunotherapies from its proprietary mRNA-based TriMix platform. eTheRNA’s goal is to commercialise these immunotherapies to deliver long lasting clinical remission to cancer patients. eTheRNA was established in January 2013 as a spin-off from the VUB university in Belgium and is backed by international life science investors.
Vrije Universiteit Brussel is an internationally oriented university in Brussels, the heart of Europe. By providing excellent
research and education on a human scale, VUB wants to make an active and committed contribution to a better society.
About UZ Brussels
UZ Brussel (University Hospital Brussels) has a staff of more than 3,800 employees. It is attached to the Faculty of
Medicine and Pharmacy of the Free University of Brussels on the Brussels Health Campus in Jette. With 721 hospital
beds, it accounts for 31,501 admissions of patients each year from Belgium and abroad, 396,234 consultations
(emergencies not included) and 75,646 patients at the emergency care. Its philosophy is founded on three principles:
Dutch-speaking, pluralist and social. As a university hospital, it also has a teaching mission and conducts scientific
research. More information can be found at www.uzbrussel.be.
HistoGeneX Laboratories is a CAP, CLIA, and BELAC-accredited global laboratory system located in Antwerp, Belgium
and Naperville, Illinois, USA. HistoGeneX serves pharma and biotech drug development sponsors worldwide.
The TriMix platform, on which eTheRNA’s immunotherapies are based, comprises three mRNAs encoding proteins (caTLR4,
CD40L and CD70) that work to deliver optimal activation of dendritic cells. These cells behave as immune response
mediators and mobilize the immune system to attack cancer cells through inducing a T-cell response. Clinical proof of
concept for TriMix-based immunotherapie