Recent progress in cancer vaccine research!

Recent progress in cancer vaccine research!   In this article, the editor compiled a number of important research results to jointly interpret the new progress that scientists have made in the field of cancer vaccine research and development, and share with you!

[1] Nature is heavy: the first case of brain cancer patient vaccinated with mutant protein vaccine shows safe and effective

doi: 10.1038/s41586-021-03363-z

Surgical resection is one of the main methods of clinical tumor treatment, and residual micro tumor tissue or circulating tumor cells can cause tumor recurrence or metastasis, which is also a major challenge for tumor treatment. Tumor vaccines can inhibit tumor recurrence and metastasis by activating continuous anti-tumor immune protection effects, and have great potential in tumor postoperative treatment. Doctors and cancer researchers from Heidelberg and Mannheim conducted a clinical trial for the first time to test a mutation-specific vaccine against malignant brain tumors; the relevant research results were published in the journal Nature, and the research results show that the vaccine is safe , And trigger the required immune response in the tumor tissue.

Diffuse gliomas are usually incurable brain tumors that spread to the entire brain and are difficult to completely remove by surgery. Chemotherapy and radiotherapy often have limited effects. In many cases, diffuse gliomas have a common feature: in more than 70% of patients, tumor cells have the same genetic mutation. The same error in the DNA causes a single, specific protein building block to be exchanged in the IDH1 (isocitrate dehydrogenase 1) enzyme. This creates a new protein structure, the so-called neo-epitope, which can be recognized as a foreign body by the patient’s immune system. The researchers stated, “Our idea is to support the patient’s immune system and use vaccines as a targeted way to alert it to tumor-specific new epitopes. The IDH1 mutation is a particularly suitable candidate because it is Gliomas are highly specific and do not occur in healthy tissues. In addition, IDH1 mutations are the cause of the development of these gliomas, which means that vaccines against mutant proteins can fundamentally solve the problem.” The study included Among 33 patients, 1 patient (ID16) was not vaccinated due to an adverse event (fever of unknown cause) that occurred before vaccination. Therefore, 32 patients received treatment and were included in the safety data set (SDS). Twenty patients (62.5%) were males and 12 (37.5%) were females, with an average age of 40.4±8.95 years.

[2] Interpretation of Nature Medicine papers! Phase 1 clinical trials have shown that patients with melanoma have a durable anti-tumor response after 4 years of cancer vaccine

doi: 10.1038/s41591-020-01206-4

In a new study, researchers from the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Broad Institute reported that after 4 years of personalized cancer vaccine treatment for melanoma patients, this The immune response triggered by the vaccine is still strong and can effectively control cancer cells. Related research results were published in the journal Nature Medicine. These findings demonstrate the endurance of the immune response generated by the vaccine called NeoVax, which works by targeting specific proteins on the tumor cells of each patient. These researchers found that nearly four years after receiving the vaccine, the patients’ immune system cells not only actively resist tumor cells expressing these unique proteins, but also target other proteins found in these patients’ tumor cells.

Dr. Catherine J. Wu, co-author of the paper, said, “These findings indicate that personalized neoantigen vaccines can stimulate a durable immune response in patients with melanoma. The evidence we found shows that the initial targeted immune response has been in the past few years. It has been expanded over the years to provide patients with continuous protection from the disease.” The study involved 8 patients who underwent surgery for advanced melanoma but were considered to be at high risk of recurrence. . In a phase 1 clinical trial, they received NeoVax treatment within a median of 18 weeks after surgery. This vaccine is made of protein fragments called epitopes, which extend from the cell surface and act as signals from the immune system. The epitope in NeoVax comes from neoantigen, an abnormal protein on tumor cells, which can remind cells that they have become cancerous and should be destroyed. Since neoantigens are only present on tumor cells, they trigger an immune response that protects normal cells from attack.

[3] BMJ Sub-Journal: New method can improve the therapeutic effect of cancer vaccine

doi: 10.1136/jitc-2020-001046

In a recent study, researchers at Jefferson University developed a cancer vaccine that prevents gastric, pancreatic, esophageal, and colon cancer from recurring. The preclinical study paved the way for a Phase II clinical trial that is expected to be open to patients this fall. The research data in this article shows that the vaccine can produce a strong immune response in mice. The relevant research was published in the Journal of ImmunoTherapy of Cancer.

Many vaccine targets, such as tumor antigens or circulating viruses, are introduced into the immune system through the “media”. This vector introduces vaccine components into the immune system, triggers the strong immune response required for immunity, and at the same time protects humans from corresponding threats. Specifically, many vaccines (including certain COVID-19 vaccine candidates) are usually constructed using adenovirus strains as vectors or vectors.

[4] Clin Transl Immunol: Significant progress has been made in cancer vaccine research! A new vaccine is expected to treat a variety of blood cancers and solid tumors!

doi: 10.1002/cti2.1141

Recently, in a research report published in the international journal Clinical & Translational Immunology, scientists from the Australian Institute of Technology Translation Research and other institutions stated through research that after the success of preclinical research, they plan to carry out a new type of human body Clinical trials of cancer vaccines.

Researcher Professor Kristen Radford said that the new vaccine we have developed can potentially treat a variety of blood cancers and malignancies, and it is expected to become a major breakthrough in the field of cancer vaccine research! We hope that this vaccine can be used to treat a variety of blood cancers, such as myeloid leukemia, non-Hodgkin’s lymphoma, multiple myeloma, childhood leukemia, and many other solid tumors, such as breast cancer, lung cancer, ovarian cancer, and pancreas. Carcinoma and glioblastoma, etc.

[5] Sci Adv: Chinese scientists use new microcapsules to develop high-performance cancer vaccines!

doi: 10.1126/sciadv.aay7735

The use of approved materials and clever design to develop safe and effective biologics can accelerate the clinical transformation process. Scientists from the Institute of Process Engineering, Chinese Academy of Sciences have developed a new therapeutic tumor vaccine based on self-healing polylactic acid microcapsules, which can effectively activate the immune system and inhibit tumorigenesis. This study was published in the journal Science Advances. The therapeutic cancer vaccine that uses the immune system to kill cancer cells has shown great promise in tumor treatment.

The research team is led by researcher Ma Guanghui and researcher Wei Wei of the State Key Laboratory of Biochemical Engineering of the Institute of Process Engineering, Chinese Academy of Sciences. They have designed and produced a variety of tumor vaccines in their preliminary work. These vaccines have been shown to be effective against different tumor models, such as lymphoma, melanoma and breast cancer. However, due to certain restrictions, researchers are forced to improve early tumor vaccines. For example, Professor Ma said that poor immune microenvironment, complicated preparation procedures and frequent vaccination have severely affected their performance. Professor Ma said: “Therefore, we have designed a new formulation based on microcapsules for high-performance cancer vaccination.”

[6] ACS Central Sci: Chinese scientists develop personalized cancer vaccines

doi: 10.1021/acscentsci.9b01174

Therapeutic cancer vaccines were developed as early as 100 years ago, and so far there is still no effect. Before achieving concrete results, two major obstacles must be overcome. First, because tumor mutations are unique to each patient, cancer cell antigens must be targeted very precisely, which is difficult to achieve. Second, a safe system is needed to deliver the vaccine to the right place and achieve a strong and specific immune response.

Recently, the Tang Li team of EPFL School of Engineering has proposed a solution to the transportation problem. The researchers used a polymerization technique called polycondensation to develop a prototype vaccine that can automatically move to the desired location and activate the immune cells there. This patented technology has been successfully tested on mice, which is also the subject of a paper in ACS Central Science magazine. Tang Li also co-founded a start-up company called PepGene with partners, and they are working on an algorithm that can quickly and accurately predict mutant tumor antigens. The combination of these two technologies will produce a new and better cancer vaccine in the next few years.

[7] JCI: Scientists are expected to develop a more efficient cancer vaccine strategy

doi: 10.1172/JCI128267

Recently, scientists from Duke University and other institutions have used dendritic cell precursor cells as an efficient and effective method to successfully stimulate the body’s immune system to fight cancer. The relevant research results were published in the international journal Journal of Clinical Investigation; Related research results may provide alternative products for dendritic cell cancer vaccines, which can be used as a new method to promote T cells to effectively identify and attack cancer cells, but their effectiveness in improving patient survival rates is very limited.

This new method can use monocytes to function. Monocytes are a type of white blood cell and a precursor to dendritic cells. When monocytes are loaded with antigens and injected into mice, they will indirectly Induces the body’s T cell response that attacks tumor tissues. Researcher Michael D. Gunn said that this is a brand-new method. Compared with dendritic cell vaccines, it has two major advantages. First, we can observe a better immune response and anti-tumor effect; second, for manufacturing Dendritic cell vaccines need to start with monocytes, and then culture and process the cells to differentiate into dendritic cells.

[8] NEJM: HPV vaccine effectively prevents cervical cancer

doi: 10.1056/NEJMoa1917338

According to a large study published by researchers from the Karolinska Institute in Sweden in the New England Journal of Medicine, women who have been vaccinated against HPV have a significantly lower risk of cervical cancer. This positive effect is positive for women who were vaccinated when they were young. The most obvious. “This is the first time that we have demonstrated at the population level that HPV vaccination can not only prevent cell mutations that may lead to cervical cancer, but also prevent the occurrence of actual invasive cervical cancer. This is something we have long suspected.

HPV (Human Papilloma Virus) is a type of virus that usually causes genital warts and various types of cancer, including cervical cancer. This disease kills more than 250,000 women worldwide each year. More than 100 countries have implemented national vaccination plans against HPV. Previous studies have shown that HPV vaccine can prevent HPV infection, condyloma acuminatum, and precancerous cervical lesions that may develop into cervical cancer. However, there is still a lack of large population-based studies.

[9] Sci Rep: Neoantigens can improve the effect of cancer vaccines

doi: 10.1038/s41598-019-50738-4

Recently, in a new paper published in Scientific Reports, Professor Stephen Albert Johnston from Arizona State University’s School of Biodesign and his research team presented the first proof-of-concept results on a universal vaccine for cancer. They studied mutations in more than 50 cancer cell lines and 85 tissue samples from the Mayo Clinic in Arizona, as well as blood from patients with five different advanced cancer types (lung cancer, breast cancer, brain cancer, stomach cancer, and pancreatic cancer) sample.

They discovered a common new tumor mutation that can provide new clues for the design of cancer vaccines, including: 1) broadly protective or whole cancer vaccines 2) cancer type-specific vaccines (such as breast cancer and pancreatic cancer vaccines) ) 3) Personalized cancer vaccines based on individual unique mutations. In order to discover neoantigens in tumors, Johnston’s team developed a new type of chip. The chip they made can present all 200,000 possible new antigens, allowing them to simply screen for specific antibodies in the blood.

[10] PNAS: New discovery! Natural killer cells may help develop new potential cancer vaccines!

doi: 10.1073/pnas.1722374115

Recently, in a research report published in the international journal Proceedings of the National Academy of Sciences, scientists from Dalhousie University pointed out through research that natural killer cells (NK cells, natural killer cells) may develop potential cancer vaccines. key. Traditional training may teach the body to adopt a variety of complex methods to protect itself from the invasion of harmful pathogens. Two of these methods are the innate and acquired adaptive immune system. The adaptive immune system is obtained when the body is exposed to antigens. The immune protection of this kind of immune protection has a certain memory, which can make the vaccination become effective, which is why we only get measles or chickenpox once.

NK cells are a type of white blood cells belonging to the innate immune system. They can patrol the body to find harmful cells, such as cancer cells or viral infections, but they cannot effectively remember these harmful cells. Scientists have long known that T cells and B cells can give the body’s immune system long-term memory. However, when researchers began to vaccinate mice lacking these memory-activating cells, these mice began to show memory responses, which may be It can open up a whole new field of immunology research.

(source:internet, reference only)

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