The two companies, with immatics as coordinator and BioNTechas vice coordinator—and more than a dozen European, American and Israelipartners in GAPVAC—intend to conduct a multinational clinical trial treatingglioblastoma patients with such vaccines beginning in 2014. Giving them a legup is support from the European Union, to the tune of $8 million through theEuropean Union Framework 7 program grant fund.
GAPVAC is reportedly the first EU-funded initiative aimed atclinically developing biomarker-guided actively personalized vaccines (APVACs)to treat cancer patients. The consortium consists of organizations from thebiotech industry and academia with cutting-edge expertise in cancer vaccinedevelopment, and it is designed to create and develop APVACs tailored for eachpatient based on the individual aspects of the patient's tumor and immunesystem.
"Some 97 percent of all mutations in a given tumor areindividual-specific; there is much heterogeneity even in what is technicallythe same cancer from one patient to the next," Prof. Ugur Sahin, CEO ofBioNTech AG, tells DDNEWS. "BioNTechand immatics last years for the first time published proof of concept that youcan use mutations identified through next-generation sequencing to createvaccines against tumors."
"There is a lot of work that has been done at the University of Mainz and University of Tuebingen, which our two companies came out of,in the area of immunotherapy for cancer," adds Dr. Harpreet Singh, chiefscientific officer of immatics. "People are interested in vaccines for cancers,but much of the focus has been to create a vaccine for the cancer specifically.We have a vision that one should adapt the vaccine to the patient, and not thepatient to the vaccine."
According to GAPVAC's July news release about the creationof the consortium, "The latest technologies, including next-generationsequencing, high-sensitivity mass spectrometry and innovative immunomonitoringapproaches, will be combined to generate an optimal therapy for the individualpatient."
The project aims to show that APVACs are well tolerated andinduce a strong and specific immune response against cancer—in this case,glioblastoma, an aggressive form of brain cancer with poor prognosis.
At the core of the GAPVAC project is a Phase I clinicaltrial that will enroll as many as 30 newly diagnosed glioblastoma patients andis expected to start in 2014. Glioblastoma patients will be repetitivelyimmunized with a vaccine specifically prepared for them. This activelypersonalized vaccine will be administered in addition to standard chemotherapyafter surgery and initial radiochemotherapy are completed. The clinical trialwill be led by Dr. Wolfgang Wick of the University of Heidelberg and Dr.Pierre-Yves Dietrich of the University of Geneva.
BioNTech AG will add proprietary glioblastoma-expressedtumor-associated antigens to the peptide warehouse. BioNTech and immatics willuse their next-generation sequencing and mass spectrometry expertise,respectively, to identify immunogenic tumor mutations and generate a blueprintfor the personalized vaccine that will include patient-specific tumor mutatedpeptides.
The APVAC "on-demand" manufacturing will be performed by theGMP unit at the Department of Immunology led by Prof. Hans-Georg Rammensee ofthe University of Tuebingen. The complex peptide warehouse will be manufacturedby BCN Peptides in Spain, a company focused on peptide synthesis for clinicaluse.
In addition, 10 academic partners have joined the consortiumto apply the APVACs to their patients as well as contributing to the projectwith their own research. They are Eberhard Karls University of Tuebingen,Beatson West of Scotland Cancer Centre, Universities Hospital Geneva,Universities Hospital Heidelberg, Herlev Hospital, Leiden University MedicalCentre, University of Pittsburgh Cancer Institute, University of Southampton,Technion and Vall d'Hebron University Hospital.
The clinical trial will be accompanied by an extensivebiomarker program led by the Association of Cancer Immunotherapy (CIMT), anon-profit organization dedicated to the advancement of cancer vaccines, andimmatics to confirm the mechanism of action and to identify biomarker signaturecandidates predicting which patients are most likely to benefit from treatmentwith APVACs. CIMT will also act as the dissemination platform and willcontribute to the biomarker program and regulatory approach through its workingparties.
"The GAPVAC consortium is dedicated to take patient care tothe next level. This novel approach marks a fundamental paradigm shift in thetherapeutic management of cancer patients since the approach is suited toprovide a truly individualized and targeted drug development at unprecedentedspeed," says Sahin. "In fact, currently we are able to provideready-to-administer personalized drugs within three months, whereas averagetime from target-to-hit to first-in-human testing is about 5.5 years."
Echoing Sahin's enthusiasm, Singh adds, "GAPVAC representsan exciting step forward as the first project exploring actively personalizedtherapeutic cancer vaccines at a European level. Unlike other approaches, thisconsortium is looking at the specific characteristics of each patient'sdisease. If successful, this novel approach could create a completely new wayto treat cancer. Such a unique approach is only possible by combining a varietyof the latest technological innovations and by joining forces with superbbiotechnology companies and academic institutions—by partners who share adedication for the personalization of therapy for the benefit of cancer patients."