display
The pace surprised even experts: the genome of the Sars-CoV-2 coronavirus was only published a few weeks at the beginning of 2020, when companies from the USA and Germany had already presented concepts for mRNA vaccines.
Preparations from Biontech and Moderna received their first approvals as early as the end of 2020 - after studies had shown safety and effectiveness.
The rapid development of these Covid-19 vaccinations was made possible because many of the foundations for mRNA vaccines had already been laid.
The companies Biontech in Mainz and CureVac in Tübingen have been researching the approach against tumors for years.
"Many researchers already had experience with the development of mRNA-based vaccines," explains the immunologist Sebastian Kreiter from Tron, a medical research institute at the University of Mainz.
"That enabled us to react very quickly."
Ulrike Gnad-Vogt also underlines the importance of this preliminary work.
"We have been conducting clinical studies with mRNA vaccines since 2008 and have started with cancer medicine," says the medical director of oncology at CureVac.
"We learned a lot in the process, such as how to design vaccines better and more potent."
display
For mRNA-based therapies, some experts emphasize, oncology may be even better than infectious diseases like Covid-19, where millions of people receive the same vaccine.
"Against Sars-CoV-2, the mRNA vaccination cannot fully exploit all of its strengths," says Niels Halama from the German Cancer Research Center (DKFZ) in Heidelberg.
"A major advantage of the process is that it can be used to produce individual vaccines for different patients - and in a short time."
Basically, the messenger RNA (mRNA, messenger RNA) in cells ensures that information is transferred from the genetic material DNA to the protein factories.
In the case of Covid-19, the mRNA vaccination transports the construction instructions for a surface protein of the pathogen, with the help of which the body then produces the virus protein.
The body recognizes this protein as foreign, and the immune system begins to produce antibodies against it.
In the event of an infection with the Sars-CoV-2 pathogen, the body is then prepared and can quickly render the virus harmless.
In cancer medicine, the mRNA vaccination contains the blueprints for important components of a tumor, such as proteins.
The body's defense can then take targeted action against these so-called antigens.
display
“The choice of target structures is extremely important,” emphasizes Halama.
“In order to catch the tumor precisely, it should not occur in healthy body tissue if possible.” What is elegant about the approach is that the vaccination induces the body to produce the antigens itself and present it to the immune system.
That’s the theory.
How well does the approach work in practice?
“We have come a long way,” says Halama, “but the proof is still pending.
It has to be shown that this vaccination offers patients greater advantages - especially in comparison to the other therapies. "
In general, a lot has happened in cancer medicine in recent years: In addition to the major forms of therapy, surgery, chemotherapy and radiation therapy, immunotherapy has now established itself as the fourth pillar.
The developers of the most common approach - checkpoint therapy - received the Nobel Prize for Medicine in 2018.
display
Checkpoint therapy is based on the fact that certain proteins act as a kind of brake - checkpoint - preventing the immune system from fighting tumor cells.
If these brakes are released with the so-called checkpoint inhibitors, the immune cells can attack the tumor cells again.
The procedure achieves spectacular results against melanoma, for example, but only helps roughly a quarter of patients.
Cancer mortality in the EU continues to fall
Taking into account the age structure, cancer mortality has continued to decrease in the EU.
This is the result of a study that was published in the journal "Annals of Oncology".
Source: WORLD
The approach of mRNA vaccinations is broader: "It is no longer just about helping the immune system, but rather you want to boost the full competence of the immune system," says oncologist Dirk Arnold, chief physician at the Asklepios Clinic Altona.
"That is a fascinating thought."
However, unlike against Covid-19, not a single drug has yet been approved.
In Germany, the Paul Ehrlich Institute (PEI) has so far approved 29 applications for clinical trials.
Of these, 17 studies are currently ongoing or are being evaluated, the others have been completed.
The studies are testing the vaccination against a large number of tumors - for example against melanoma and renal cell carcinoma, but also against lung and prostate cancer.
According to the PEI, nine of the 17 studies are in phase 2 or 3.
In one form of this approach, patients are injected via mRNA with the blueprint for one or more proteins that are known to be important in the respective tumor variant.
Other vaccinations are individually tailored: A tumor sample is taken from a patient, the genetic material is then sequenced and analyzed for special components.
The specially produced vaccine then targets such antigens.
It takes about two to three months from the biopsy to such a vaccination, says DKFZ expert Halama.
The Hamburg oncologist Arnold will soon be testing the approach as part of an international Biontech study in colon cancer.
The study examines whether the mRNA vaccination can prevent a tumor from returning after surgical removal - a so-called relapse.
Included are patients whose blood still contains tumor genes, which is associated with a significantly increased risk of recurrence.
While the cure rate in colon cancer patients without tumor DNA in the blood is more than 80 percent, with tumor DNA it falls below 20 percent, explains Arnold.
The vaccination is now being tested on these two groups.
To reduce the risk of the tumor returning, the 200 or so patients in Europe and the USA first receive chemotherapy after the operation.
In addition, some of them then receive the mRNA vaccination with the blueprint for a protein that plays an important role in the tumor of the respective patient.
The vaccine is therefore tailor-made in each case.
Ultimately, the study examines whether the additional therapy reduces the risk of recurrence or not.
The start planned for the beginning of 2021 has been delayed due to the Corona, but Arnold expects it to start this quarter.
He expects the first results in about three years.
display
The Mainz physician Kreiter has great hope that the approach can prevent such recurrences.
"The mRNA vaccination can make a decisive contribution to the detection of micrometastases in the whole body and, hopefully, to destroy them."
According to the current state of knowledge, the side effects of the procedure are manageable.
Redness, fatigue, headache or fever were observed, experts do not expect long-term consequences.
However, the optimal procedure is still open - i.e. how often the vaccinations have to be repeated.
"There is still no gold standard for the frequency and interval between mRNA vaccinations," says Kreiter.
"We're breaking new ground."
Such vaccinations are also tested against advanced tumors.
For example, the Ludwig Institute for Cancer Research in the USA is testing an mRNA vaccine from CureVac against metastatic lung cancer together with the pharmaceutical company Boehringer Ingelheim.
In this phase 1/2 study, according to Gnad-Vogt, up to 56 patients receive an mRNA vaccination in combination with two checkpoint inhibitors.
The vaccine contains blueprints for six tumor proteins and is initially injected into the skin once a week and later at several weekly intervals.
"The checkpoint inhibitors are intended to increase the immune response triggered by the vaccination," says Gnad-Vogt.
The reinforcing effect of such a combination is shown by interim results of a phase 1 study on 89 patients with advanced melanoma, which a team led by Biontech founder Uğur Şahin presented in the summer in the journal "Nature".
Participants received at least eight mRNA vaccinations that contained blueprints for four common melanoma antigens.
The interim results confirm a strong immune reaction, especially in that part of the patients who also received checkpoint therapy.
In a third of this group, the tumors shrank.
“These data are very promising,” says co-author Kreiter.
Combinations of mRNA vaccinations with checkpoint inhibitors, chemotherapy or radiation therapy are important in order to gain experience, says Halama.
“You have to learn what works and what doesn't.” PEI President Klaus Cichutek adds: “At the moment, mRNA immunotherapy is primarily thought of as an additional treatment, because the effects of the immune system that it stimulates are relatively mild.”
Similar to the way Covid-19 research has benefited from oncological research, the vaccination campaigns that have started are now giving mRNA vaccinations against cancer a boost.
"We are now learning a lot very quickly about tolerability and the immune responses triggered by the mRNA vaccination in a very large number of people," says CureVac expert Gnad-Vogt.
The approach of the mRNA vaccination is literally "catapulted forward", emphasizes the DKFZ researcher Halama.
The Hamburg doctor Arnold hopes that mRNA vaccinations will significantly improve cancer medicine, but warns against exaggerated expectations: "That will not be the key to curing all types of cancer, I am sure."
PEI President Cichutek hopes "in the best case" with approvals within a period of the next five years, but emphasizes that this hope is "a speculation".
"As the Paul Ehrlich Institute, we have become very careful."