Prof. Dr. Juliane Walz is researching cancer vaccines at the University of Tübingen. The key: tumor-specific peptides that activate the T-cells in the fight against the tumor. But can the vaccine save 15-year-old Marlene?
The moment of hope lasts only a few seconds. Marlene*, 15 years old, is waiting on a couch in the Clinical Cooperation Unit (CCU) Translational Immunology of the Medical Clinic at the University Hospital of Tübingen for the injection. She will be the first to be vaccinated against fibrolamellar hepatocellular carcinoma - a rare liver cancer that mainly affects young people. It is an individualized attempt at a cure. Only possible because other therapies have so far failed. A last chance.
Vaccination against cancer
Juliane Walz, Professor of Peptide-Based Immunotherapy and Medical Director of KKE Translational Immunology, applies the needle to Marlene's lower abdomen. A prick, a plaster - that's it. In four weeks there will be the first examination, then she will also receive the second vaccination. Then they will know more about whether it has worked. Peptide-based immunotherapy is a new and promising approach in which tumor-specific peptides are used to activate the T cells as highly effective defense cells of the immune system. "Our goal is to develop vaccines for tumor patients," says Juliane Walz. "We want to improve the prognosis of tumor patients". In her department for peptide-based immunotherapy at the University Hospital of Tübingen, she and her team are therefore searching for tumor-specific peptides.
Tissue samples are dissected with a scalpel in the cold room at minus four degrees, crushed and filtered overnight. Sometimes they find thousands of different peptides, sometimes up to ten thousand. But which ones are so specific to the respective tumor that the T cells are activated? It is the proverbial search for a needle in a haystack.
A match with peptides that have already been found on tumor tissue and never on healthy tissue is a hit. In the case of fibrolamellar carcinoma, doctoral student Jens Bauer came across promising peptides in the laboratory. "The special thing about this rare form of liver cancer is a gene fusion," explains Juliane Walz. This means that a specific fusion protein - the DNAJB1-PRKACA fusion protein - is found in all patients.
Four weeks after Marlene's vaccination, her blood is examined for these T-cells. The characteristic hardening has already formed at the injection site, similar to an additional lymph node. A good sign. Due to the special formulation of the vaccine, the vaccine remains localized at the vaccination site. This means that the immune cells migrate to the injection site, so to speak, and then back into the blood and to the tumor.
But Juliane Walz can hardly find any T-cells in the laboratory. The problem: Marlene is taking immunosuppressant medication to prevent her body from rejecting the donor liver she received due to the advanced stage of the tumor. She cannot stop taking the medication.
Juliane Walz was nevertheless confident. "The requirements were all met" she says. All the tests before the vaccine was produced were positive. The peptides from the fusion protein elicited a T-cell response. An adjuvant was added to the vaccine to potentiate the effect. But Juliane Walz also knows that this is just a trial - the preliminary stage before clinical trials.
And yet, there is no getting around the hope. If the therapy worked, Marlene would not be the only one to recover. Four weeks after the first vaccination, Marlene receives the second dose. Her blood is tested again. Juliane Walz and her colleagues analyze the samples in the laboratory: This time the immune system has reacted. There is a strong T-cell response.
So strong that Marlene has not had any relapses to date - that was three years ago. She was able to finish school and is currently doing a voluntary social year. She can live. Based on these encouraging results, the fusion-based peptide vaccine is currently being tested in a Phase I clinical trial in combination with the immune checkpoint inhibitor atezolizumab (provided by Roche).
Not only patients with fibrolamellar carcinoma were included in the study, but also people with tumors of the pancreas and bile ducts. This is because the DNAJB1-PRKACA fusion protein has now also been discovered there. The study is funded by the Else Kröner-Fresenius Foundation, the Center for Rare Diseases and the Medical Faculty of Tübingen.
* Name changed