There is a new vaccine for malignant brain tumors! Early trials are safe and effective (with introduction of other brain tumor vaccines)

This article is converted Medicine original, reproduced please indicate the source Author: Yun Introduction: In Germany, every year about 5,000 people diagnosed with glioma, of which about 1200 cases are IDH1 mutation of diffuse glioma.

So far, we have generally only had limited success in preventing tumor progression in these patients.

We believe that the IDH1 vaccine offers the potential to develop treatments that can effectively suppress these tumors in the long term.

Glioma is the most common malignant primary brain tumor.
It is the primary brain tumor with the highest incidence at present, accounting for nearly a quarter of all primary brain tumors and a quarter of all malignant tumors three.

Glioblastoma (or glioblastoma multiforme) is the most common and aggressive type of glioma, accounting for more than half of all gliomas.

For this kind of tumor, there is currently no cure, and treatment is very difficult: one is because glioblastoma will extend its antennae into the brain instead of forming a solid mass that the doctor can target and remove, so I want to remove them completely.
Impossible; second, because the brain has a protective layer called the blood-brain barrier, most anticancer drugs cannot reach the brain tumor.

Therefore, new treatment methods are urgently needed in clinic.

Vaccines are the best way for humans to prevent diseases before they occur.

Recently, the German Cancer Research Center, Heidelberg National Cancer Center (NCT) Michael Platten team developed a tumor vaccine (IDH-vac) that targets IDH1 mutations.

This tumor vaccine can effectively activate the anti-tumor immune response in the patient's body and exert an anti-tumor effect.

The research results were published in the top journal "Nature", entitled "A vaccine targeting mutant IDH1 in newly diagnosed glioma".

Source: "Nature" Mutations in the tumor genome usually lead to protein changes typical of cancer.

The vaccine can alert the patient's immune system to these mutated proteins.

Scientists recently completed a clinical trial for the first time to test a mutation-specific vaccine against malignant brain tumors.

The results prove that this vaccine is safe and can trigger the desired immune response in tumor tissues.

Studies have shown that in many cases, diffuse glioma has a common feature: in more than 70% of patients, tumor cells have the same genetic mutation.

The same error in the DNA causes the exchange of a single specific protein building block in the IDH1 enzyme, which creates a new protein structure called neo-epitope, which can be recognized as a heterologous by the patient's immune system.

Platten's team had obtained artificial versions of IDH1 protein fragments with characteristic mutations several years ago.

This mutation-specific peptide vaccine can prevent the growth of IDH1 mutant cancer cells in mice.

In 2019, Platten won the German Cancer Prize for this discovery.

At present, preventive and therapeutic vaccines developed for various types of cancer have come out one after another, becoming a new weapon that can prevent the progression of the disease, prevent recurrence, and even serve as a treatment method to help humans overcome cancer.

Encouraged by these results, Platten and a team of doctors decided to test a mutation-specific vaccine in patients newly diagnosed with IDH1 mutant gliomas (WHO grades III and IV astrocytomas) for the first time in a phase I study.

The study was attended by 33 patients from several different centers in Germany.
The study was supported by the Heidelberg National Cancer Center (NCT) and the Neuro-Oncology Working Group (NOA) of the German Cancer Society.

In addition to standard treatment, they also received peptide vaccine treatment.

In any patients who have been vaccinated, doctors have not observed any serious side effects.

In 93% of patients, the immune system shows a specific response to vaccine peptides.
Regardless of the patient's genetic background, the immune system shows a specific response.
The genetic background determines the important presentation molecule HLA protein of the immune system.

The study showed that in fully vaccinated patients, the three-year survival rate after treatment was 84%, and in 63% of patients, the tumor did not develop during this period.

Among the patients whose immune system had a specific response to the vaccine, a total of 82% of patients had no tumor development within three years.

 Although Professor Michael Platten of the research team said: "Without a control group, we cannot draw any further conclusions about vaccine efficacy from this early study.

" However, the results of this phase I clinical study have been preliminarily confirmed.
The safety, tolerability, and effectiveness of this tumor therapeutic vaccine targeting the neoantigen IDH1 (R132H) provides the potential to develop a more effective and longer-term treatment method to inhibit these tumors, and provide a broad brain Patients with glioma brought the dawn of hope.

In this follow-up study, the team combined the IDH1-vac vaccine with checkpoint suppression immunotherapy.

The researchers are also preparing for a phase II study, hoping to check for the first time whether the IDH1-vac vaccine produces a better therapeutic effect than standard treatment alone.

 What is a cancer vaccine? Because there are special proteins on the surface of cancer cells, cancer vaccines target these proteins, and then the immune system can specifically eliminate cancer cells without harming normal cells.

Classification of cancer vaccines The current cancer vaccines are divided into: preventive cancer vaccines and therapeutic cancer vaccines.

Preventive cancer vaccine Human papillomavirus (HPV) vaccine can prevent cervical cancer, anal cancer, laryngeal cancer, vagina cancer, vulvar cancer and penile cancer related to HPV infection; HBV vaccine prevents liver cancer related to HBV infection.

Cancer Vaccine Sipuleucel-T (Provenge): the first therapeutic dendritic cell vaccine approved by the FDA for the treatment of advanced prostate cancer resistant to hormone therapy; Talimogene laherparepvec (T-VEC): the first oncolysis approved by the FDA Viral vaccine for the treatment of advanced melanoma.

It is made from the herpes virus, which can produce cytokines, strengthen the immune system, and cause flu-like symptoms in a short time.

Therapeutic cancer vaccines are mainly divided into: tumor whole cell vaccine dendritic cell (DC) cancer vaccine protein peptide vaccine gene vaccine brain tumor vaccine-NeoVax neoantigen vaccine NeoVax, which was first created by Dana-Farber MD Catherine Wu.

NeoVax is a personalized experimental neoantigen vaccine designed to recognize cancer-specific proteins (ie neoantigens), which are proteins that are specifically present in cancer cells but not on normal cells.

Clinical trials are currently being carried out in brain tumors, kidney cancer, and melanoma.
The clinical data of brain tumors show that the median progression-free survival period is 16.
8 months.

This research is also in early 2021 and has just been published in the international blockbuster cancer journal "Nature medicine".

Brain tumor vaccine-SurVaxMSurVaxM, also known as SVN53-67 / M57-KLH, is an immunotherapy and the world's first peptide mimicking tumor vaccine.

This is a peptide vaccine that targets survivin, a protein that helps cancer cells grow uncontrollably.

A study of patients with glioblastoma brain cancer found that the life expectancy of vaccinated people was about twice as long as expected.

 The median overall survival time for patients receiving SurVaxM was 30.
5 months, compared with 14.
8 months for patients receiving standard care.

The current phase II clinical studies of the drug show that the immunotherapy SurVaxM vaccine is safe, well tolerated, and can prolong survival even in the most difficult-to-treat patient subgroup.

Since this is a synthetic vaccine, it is made of natural amino acids and decomposes during an immune response, so the side effects are minimal.

MimiVax's SurVaxM vaccine was invented by Roswell Park and was awarded the orphan drug designation by the U.
S.
Food and Drug Administration (FDA) in 2017.

Brain tumor vaccine-IGV-001 IGV-001 starts with collecting tumor cells surgically removed from GBM patients, and then is treated with IGF-1R antisense oligonucleotides (IMV-001) to push tumor cells to controlled cell death.

Finally, these treated cells were mixed again with an excess of IMV-001 (as an adjuvant) and placed in the infiltration chamber, and finally implanted in the patient's abdomen within 24 hours after the operation.

After the implantation time reaches 48 hours, take it out to complete the whole process of vaccination.

This innovative vaccine has been granted orphan drug designation by the US FDA.

At the 2019 American Association for Cancer Research Annual Meeting (AACR 2019), Imvax announced the interim results of a phase 1b clinical trial of IGV-001 for the treatment of GBM.
The results showed that: among newly diagnosed GBM patients, receive IGV-001 treatment Of patients’ overall survival (OS) and progression-free survival (PFS) are better than those of patients receiving standard treatment.

In addition, the final test results completed in May 2020 also confirmed the efficacy of IGV-001.

The company expects to conduct a phase 2 clinical trial of IGV-001 for the treatment of newly diagnosed GBM patients in early 2021.

Brain tumor vaccine-DC (dendritic cell) vaccine On April 14, 2017, a phase I clinical study of 11 patients with glioblastoma found that after the patients received the combined treatment of the DC vaccine under investigation and temozolomide, Its survival period exceeds five years, and the relevant test results are published in the journal "Clinical Cancer Research".

Brain Tumor Vaccine-Zika Live Attenuated Vaccine In 2017, Qin Chengfeng's team from the Academy of Military Medical Sciences and collaborators jointly discovered that Zika virus can specifically infect and kill neural precursor cells and neural stem cells, and therefore developed different types of Zika.
Cardiac attenuated live vaccine.

Experiments have shown that the vaccine strain is also very safe for intracranial injection, will not cause any neurological symptoms and behavioral abnormalities, and its neurovirulence is lower than the currently widely used Japanese encephalitis vaccine.

The research was published online in mBio, an authoritative journal of the American Society for Microbiology, on September 18, 2018.

Brain tumor vaccine-dendritic cell vaccine DCVax-L Northwest Bio, which focuses on the development of personalized cancer vaccines, has announced the results of a phase III clinical trial, showing that the dendritic cell vaccine DCVax-L improves the newly diagnosed glioblastoma The survival rate of patients with cell tumors, the longest survival period of more than 3 years, has exceeded 2 to 3 times that of standard treatment.
The relevant data is published in the Journal of Translational Medicine.

The study found that patients from the two groups had a median survival time of 23.
1 months after surgery.
Compared with the standard treatment alone in the previous study, the median survival time was extended by 8 months.

In 2015, the British Medical and Healthcare Products Regulatory Agency (MHRA) awarded DCVa xL the "Potential Innovative Medicine" (PIM) qualification.

The DCVa xL vaccine is the first "potential innovative drug" granted by the MHRA since the launch of the "New Drug Trial Program" (EAMS) new policy in April 2015.

This innovative drug is considered to be the British version of the "breakthrough drug" review.

Conclusion I believe that more and more new treatment technologies and new drugs will emerge in the near future to prevent and treat refractory glioblastoma.

Reference materials: [1] https://medicalxpress.
com/news/2021-03-first-ever-vaccine-malignant-brain-tumors.
html [2] 021-03363-z Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options.

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