Therapeutic vaccines: Top 10
10 promising therapeutic vaccines
Svetlana Shchegol, "Weekly Pharmacy" www.apteka.ua
The practice of vaccination began when, in 1796, Edward Jenner successfully vaccinated an 8-year-old boy against smallpox. Since that time, many vaccines have been created that have brought mankind relief from various diseases. For many years, vaccines have been associated with the prevention of infectious diseases. But recently, the attitude towards them as an exclusively preventive remedy has changed. Therapeutic vaccines have appeared that induce an immune response in patients and thereby contribute to the recovery or improvement of their condition. Such vaccines are used for chronic diseases caused by bacteria or viruses, malignant neoplasms, allergic or autoimmune pathology.
The first vaccine used for malignant neoplasms was approved in 2008. After that, scientists began to explore the possibility of creating a vaccine against pancreatic, lung, brain, cervical cancer, as well as against HIV/AIDS, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, melanoma. The following are 10 promising therapeutic vaccines.
The GVAX antitumor vaccine of BioSante Pharmaceuticals was developed for the treatment of pancreatic cancer, consists of irradiated autologous tumor cells genetically modified in such a way that they are able to influence the synthesis of an immunostimulating granulocyte-macrophage colony-stimulating factor.
Phases I-II of clinical trials of this vaccine have been completed, during which it demonstrated antitumor activity against 5 types of malignant neoplasms, such as melanoma, prostate, pancreatic, lung, kidney cancer.
An important advantage of the GVAX vaccine is that its creation does not require the isolation of specific tumor antigens.
According to the results of studies presented in March 2012 at the symposium on malignant neoplasms of the gastrointestinal tract (Gastrointestinal Cancers Symposium), the survival rate of patients with pancreatic cancer who received the GVAX vaccine increased by 60%. Side effects were mainly reduced to local reactions at the injection site.
The vaccine for the treatment of pancreatic and lung cancer HyperAcute Pancreas produced by NewLink Genetics consists of a group of allogeneic tumor cell lines of pancreatic cancer.
With intradermal injection, approximately 150 million cells of the HyperAcute Pancreas vaccine line enter the human body.
In October 2012, phase III of an open randomized clinical trial involving patients with operable or inoperable pancreatic cancer began. The primary endpoint of a clinical trial is to assess the overall survival of patients with pancreatic cancer. The secondary endpoint is the assessment of disease progression–free survival and immune response.
The immunotherapy vaccine Rindopepimut from Celldex Therapeutics has shown a positive result in increasing the survival rate of patients with newly diagnosed glioblastoma, one of the most aggressive forms of brain tumor.
The vaccine acts on the mutated form of the epidermal growth factor receptor (epidermal growth factor receptor).
The life expectancy of patients with glioblastoma is about 15 months after the detection of a malignant neoplasm. The results of the vaccine studies showed that the average life expectancy of such patients reached 24 months. Consequently, the Rindopepimut vaccine prolongs the life of patients after the diagnosis of the disease by almost 2 times. Preparations are underway for phase III clinical trials of the vaccine. Rindopepimut is generally well tolerated. Side effects were manifested mainly by a reaction at the injection site, fatigue, skin rash, nausea were noted in some patients.
Inovio Pharmaceuticals' experimental vaccine VGX-3100 activates the body's immune response to protect against HPV-16 and HPV-18 human papillomavirus, which is the cause of 70% of cases of cervical cancer.
The vaccine contains synthetic DNA molecules that are embedded in the genetic material of the patient's cell and stimulate an immune response against cells infected with the human papillomavirus.
According to the results of studies published in the journal ScienceTranslationalMedicine, 18 women participating in the study had an immune response after a 3-time administration of the VGX-3100 vaccine. In 14 women (78%), the vaccine stimulated an increase in the number of T cells responsible for cellular immunity.
Currently, phase II clinical trials of VGX-3100 are being conducted with the participation of 150 women, the results of which are expected in 2013.
The PENNVAX-B vaccine from Inovio Pharmaceuticals for the treatment and prevention of HIV infection contains DNA fragments encoding HIV proteins. To penetrate DNA fragments into cells, the electroporation method is used – the creation of pores in a bilayer lipid membrane under the action of an electric field.
In phase I of the PENNVAX-B trials, 12 patients with HIV undergoing highly active antiretroviral therapy were vaccinated 4 times for 16 weeks. According to the interim results, the formation of a T-cell immune response was noted in at least half of these patients.
In 2008, the US National Institutes of Health allocated $23 million to VGX Pharmaceuticals. US$ to complete the development and production of the PENNVAX-B vaccine. In the same year, VGX Pharmaceuticals and Inovio teamed up to complete research on an experimental vaccine for the treatment and prevention of HIV infection.
The Novartis and Cytos CAD106 vaccine was developed to treat patients with Alzheimer's disease, the cause of which, according to one of the common hypotheses, is the formation of beta-amyloid plaques in brain cells.
The mechanism of action of the vaccine is to produce antibodies to beta-amyloid without activating a specific type of T-cells.
Phase I clinical trials involved patients aged 50 to 80 years with moderate severity of the disease. During the study, the first group of participants received subcutaneous injections of 50 mcg CAD106, the second – 150 mcg, and the third was administered a placebo. Each patient from the first and second groups received 3 subcutaneous injections. To assess the safety profile of CAD106, patients underwent magnetic resonance imaging, electrocardiography, electroencephalography, and also used various types of physiological and neurological testing. As a result of injections, 80% of patients began to develop antibodies to beta-amyloid, which persisted for 3 years.
CureVac researchers have developed the CV9201 vaccine against non-small cell lung cancer, which accounts for up to 80% of all lung malignancies.
Due to the adjuvant properties of mRNA, which is part of the vaccine, it activates cellular immune responses.
According to the results of CV9201 studies, an immune response was formed in 65% of patients after its 5-time administration. Moreover, activation of both cellular and humoral immune responses was noted. The reaction of the immune system to the introduction of the antigen directly correlates with an increase in the 5-year survival rate of patients. Therefore, the researchers suggested using the determination of the level of activation of the immune response to predict possible treatment outcomes.
Dietmar Hopp, the founder of SAP, provided $104 million to CureVac. for the development of RNA technology, in particular for the development of a vaccine against prostate cancer.
Specialists of the pharmaceutical company "Bavarian Nordic" reported that the combination of Prostvac vaccine with ipilimumab can increase the clinical effectiveness of the treatment of melanoma in the late stages. In the USA, ipilimumab was approved in early 2011. The Prostvac vaccine contains human DNA to enhance the body's immune response.
Studies of this vaccine were conducted at the Universities of Southampton (University of Southampton) and Surrey (University of Surrey), the Royal Marsden Hospital, the Cancer Research UK in Leeds. They were attended by 30 patients who underwent 7 subcutaneous injections for 5 months.
The purpose of this study was primarily to determine the safety profile of the drug. Reiner Laws, president of the Bavarian Nordic company, suggests that a license for marketing this vaccine will be obtained in 2015.
In the course of randomized trials of the efficacy and safety of the experimental NeuVax vaccine of Galena Biopharma for the treatment of HER2-positive breast cancer in the early stages, encouraging results were obtained.
The mechanism of action of NeuVax is to activate the immune response of the body due to the fragments of the HER2 protein and granulocyte-macrophage colony stimulating factor included in the vaccine.
The study involving 163 patients was conducted for an average of 30 months. Patients whose malignant neoplasm of the breast was characterized by HER2+ received NeuVax adjuvant therapy. During the study, a significant decrease in the frequency of relapses of the disease was noted. In patients with HER2–who were given the NeuVax vaccine, not only the recurrence rate decreased, but also the mortality rate – 0% compared to 20% in those who did not use the vaccine.
The data obtained during the research can be useful for more than 50% of patients with breast cancer, whose malignant neoplasm belongs to the HER2-group, when trastuzumab is not being treated.
In November 2011, Galena Biopharma signed an agreement with Genentech, a member of the Roche Group, the condition of which is the joint financing of a Phase III study involving 700-1000 patients for whom trastuzumab treatment is not indicated.
Immatics Biotechnologies has developed a new IMA901 vaccine designed to treat patients with kidney cancer.
The researchers note that they managed to discover 2 special key biomarkers. They are supposed to indicate in which of the patients vaccination will lead to the most positive results.
The new vaccine is therapeutic, not preventive. This means that it is not used for preventive purposes, but only in cases when the patient has been diagnosed with kidney cancer. IMA901 contains 10 synthetic peptides characteristic of tumor cells that stimulate the immune response in patients with kidney cancer. Phase III of vaccine research is currently underway. The first results are expected in 2014, and the final results are expected in early 2015.
Progress in molecular biology has opened up opportunities for the development of new approaches to the treatment of patients with malignant neoplasms, chronic diseases caused by bacteria or viruses, allergic or autoimmune pathology. Today, many therapeutic vaccines are being studied in the world, and their effectiveness can be assessed in the coming years. It should be noted that vaccines have great potential and can become an important tool in preserving the health of patients with diseases that until recently were considered incurable.
Portal "Eternal youth" http://vechnayamolodost.ru10.12.2012