Brain Tumor Vaccine
Brain Tumor Vaccine have the potential to aid the body’s fight against disease. In cancer, mutations in the tumour genome can lead to alterations in protein expression that are characteristic of the disease. These altered proteins can be detected by a vaccination. To test a vaccine versus malignant brain tumors for the first time, doctors and medical researchers from Heidelberg & Mannheim conducted a clinical experiment this year. A study published in the journal Nature shows that the vaccine was safe and induced the expected immune response in tumour tissue.
Brain Tumor Vaccine: The German Cancer Research Center, University Medicine Mannheim, Heidelberg University Hospital, as well as the National Center for Tumor Diseases (NCT) Heidelberg have issued a joint press statement on this topic.
A diffuse glioma is a type of cancerous tumour of the brain that has migrated to other parts of the body and is difficult to remove surgically. It is not uncommon for chemotherapy and radiotherapy to have only a small impact. Diffuse gliomas often have one thing in common: the tumour cells in over 70% of patients carry the very same gene mutation. The IDH1* enzyme has a single, unique protein building block exchanged due to an identical mistake in the DNA. As a result, the patient’s immune system can identify the neo-epitope as a foreign protein structure.
Study director Michael Platen, Medical Director of Neurology of University Medicine Mannheim & Head of Division at the German Cancer Research Center, explained that the goal of the study was to support patients’ immune systems and to use vaccines as a targeted way to alert them to the tumor-specific neo-epitope (DKFZ). In this case, the IDH1 mutation is just a particularly strong contender because it only occurs in gliomas and is absent from healthy tissue. And because these gliomas emerge from an IDH1 mutation, “we can get to the base of the problem” by developing an IDH1 vaccination, explained Dr. Platten.
Preclinical Data Look Promising
It has been several years since Platten’s team created an artificial replica of the IDH1 protein segment with the distinctive mutation. In mice, this IDH1-mutated cancer cell-killing peptide vaccination was effective. For this finding, Platten received the German Cancer Prize in 2019.
As a result of these positive outcomes, Platten and his colleagues decided to conduct a phase I study with patients who had just been diagnosed with IDH1-mutated glioma and test the mutation-specific vaccination for the first time (WHO grades III and IV astrocytoma’s). Study participants came from a variety of medical facilities across Germany, including the National Cancer Center (NCT) Heidelberg and the German Cancer Society’s Neurooncologist Working Group (NOA). It was developed by Michael Schmitt, head of cellular immunotherapy at Heidelberg University Hospital, & Stefan Stevanovi, professor of molecular immunology at the University of Tübingen’s Department of Immunology in Heidelberg, in addition to the normal treatment. 30 patients’ immunological responses were studied.
Patients who received the vaccine had no major side effects, according to the doctors. 93% of patients’ immune systems responded to the vaccination peptide in a specific way, regardless of the surgeon’s genetic background, which defines the immune system’s essential presentation molecules, or HLA proteins.
Swelling induced by a host of invading immune cells can be seen in many patients who were vaccinated, and this phenomenon is known as “pseudoprogression.” Single cell sequencing revealed that these individuals had a substantial number of T helper cells on their blood that had specific immunological receptors that responded to the vaccine peptide. DKFZ immunologist Theresa Bunse said, “We were able to show that the engaged mutation-specific immune cells has now penetrated the brain tumour tissue” in her paper.
While 84% of patients were still alive after three years of treatment, just 63% of those who had been fully vaccinated were still cancer-free. Some 82% of patients whose immune systems responded positively to the immunizations experienced no tumour development over the course of three years.
Concept of a vaccine is being pursued
Remarking on the lack of a control group, Michael Platten said, “We cannot draw any additional inferences regarding vaccine efficacy from this early study.” As a result of the vaccine’s safety and immunogenicity, we decided to move forward with a Phase I research on the vaccine. Immunotherapy with checkpoint inhibitors is being used in conjunction with the IDH1 vaccination in this follow-up investigation. “Immune support is provided by checkpoint inhibitors. It’s possible that they’ll be able to stimulate the immune cells against by the gliomas to an even higher extent.” The German Cancer Consortium is helping to fund and implement the research in conjunction with other German institutions (DKTK).
Brain Tumor Vaccine: In addition, researchers are planning a phase II study to see if the IDH1 vaccination is more effective than standard treatment alone in terms of achieving superior treatment outcomes. “Approximately 1,200 persons in Germany each year are diagnosed with diffused gliomas with just an IDH1 mutation, which is the most common form of the disease. This is the first time we’ve been able to completely arrest the progression of tumours in these patients. We believe the IDH1 vaccination has promise for the development of a medication that can more effectively and permanently reduce these malignancies “Medical Director of Heidelberg University Hospital’s Neurological Clinic and Division Head at DKFZ, said study co-director Wolfgang Wick.