New EU-Funded Consortium Aims To Develop Targeted Cancer Vaccines
This article was originally published in The Pink Sheet Daily
Executive Summary
A clinical trial is expected to start in the U.S. and Europe in 2014 of an individualized approach to developing a cancer vaccine for glioblastoma patients.
The EU is to fund a 14-member group of biotech companies and clinical centers in Europe and the U.S. in an effort to develop a more sophisticated, personalized, approach to the development of cancer vaccines.
The 28-nation bloc is providing €6 million ($7.7 million) through the EU's Framework-7 grant program for the Glioma Actively Personalized Vaccine Consortium (GAPVAC), which will be supplemented by other funding, some of it from the institutions and companies involved.
Developing a vaccine for cancer has been a favored research strategy for pharma and biotech companies alike, although so far it has only really come up trumps in a handful of cases, like the cervical cancer vaccines, GlaxoSmithKline PLC's Gardasil and Merck & Co. Inc.'s Cervarix, and the activated cell immunotherapy, Dendreon Corp.’s Provenge.
But the success of targeted immunotherapies like Bristol-Myers Squibb Co.'s melanoma therapy, Yervoy (ipilimumab), has led to companies like Merck KGAA boosting its activities in the sector (Also see "Melanoma Success Paves Way For Path Of Gold In Cancer Immunotherapy" - Pink Sheet, 10 Jun, 2013.). Others include Amgen Inc., Biovest International Inc. and Advaxis Inc. (Also see "Sign Of The Times: Late-Stage Cancer Vaccines On Display At ASCO" - Pink Sheet, 18 May, 2012.).
Further back in development are companies like Germany’s CureVac AG which is evaluating vaccines for prostate cancer (Also see "German Billionaire Dietmar Hopp Backs CureVac Further" - Pink Sheet, 17 Sep, 2012.). The U.K's Scancell Ltd. is working on DNA plasmid vaccine for melanoma (Also see "ScanCell’s DNA Plasmid-Cancer Vaccine Shows Promise In Melanoma" - Pink Sheet, 6 Dec, 2012.). And the U.S.'s Gradalis Inc. is developing a tumor cell-based cancer vaccine [See Deal].
Personalization Is Key
The EU GAPVAC consortium wants to take personalization "to a new level", according to coordinator Harpreet Singh, who is also chief scientific officer of one of the three biotech companies in the consortium, the German company Immatics Biotechnologies GMBH. The two other companies are BioNTech AG, which will provide biomarker data, and Barcelona, Spain-based BCN Peptides SA, which will manufacture the libraries of peptides.
The approach explored first by the researchers will involve analyzing all the immunogenic peptide biomarkers expressed by tumors in each individual patient, comparing them with what is known already about the immunogenicity of similar peptides in the researchers' data banks, and selecting peptides to be included in a potential vaccine in that particular patient.
"'Tailor-made vaccines' is perhaps a better description for the approach, which will look at thousands of cancer biomarkers using sophisticated next-generation sequencing (NGS) techniques," Singh said in an interview.
Exploring The Mutanome
A second approach to personalized cancer vaccines will also be explored by the consortium, involving sequencing the genome of cancer cells in order to produce a "mutanome" – the identity of all mutations in a cancer. Comparison with the patient’s non-cancer cell genome will flag up patient-specific, tumor-related peptides.
This work will provide a blueprint for selecting the right immunogenic peptides required for a vaccine, around 10 of which will be selected from the peptide warehouse of Immatics's tumor-associated peptides (TUMAPs) and BioNTech's proprietary glioblastoma-expressed tumor-associated antigens.
Glioblastoma - the most common and most aggressive malignant primary brain tumor in humans - was selected as the cancer in which to pilot the personalized vaccine approach because it’s a rare disease, there is an unmet clinical need for an effective therapy, and few pharmaceutical companies currently have projects in the sector, Singh said.
The €6 million in funding should be sufficient to conduct a 30-patient Phase I clinical trial to test the concept, he added.
Ten academic partners from Europe and the US have joined the consortium to apply the biomarker-guided actively personalized vaccines, or APVACs, to their patients as well as contributing to the project with their own research. These are Eberhard Karls University Tuebingen (Germany), Beatson West of Scotland Cancer Centre (Scotland), Universities Hospital Geneva (Switzerland), Universities Hospital Heidelberg (Germany), Herlev Hospital/ Rigshospitalet (Denmark), Leiden University Medical Centre (The Netherlands), University of Pittsburgh Cancer Institute (US), University Southampton (UK), Technion (Israel) and Vall d’Hebron University Hospital (Spain). Clinical results from the trial are expected in 2016.
Immatic's Business Model
The therapeutic approach appears time consuming and perhaps difficult to pursue outside of a research setting. It’s certainly different to the approach currently being used by Immatics, which is developing a single allogeneic cancer vaccine by identifying cancer-related peptides that are commonly present in many patients (Also see "Immatics Raises €54 Million Series C To Fund Pivotal Therapeutic Cancer Vaccine Trial" - Pink Sheet, 21 Sep, 2010.)
But Singh suggested there might be a cost-effective business model for personalized cancer vaccines.
If a large number of immunogenic peptides were pre-manufactured and stored in a chemical warehouse or storage facility, then individualized vaccines might be quickly made just by picking out the right peptides based on biomarker information from the patient.
Ultimately, the business model must be driven by the science and the clinical efficacy. “If the science suggests a step-change in clinical efficacy, it will drive adoption of the approach,” Singh said.