Why is the new antigen vaccine likely to be the next major breakthrough in cancer immunotherapy?

In July 2017, nature, a British science journal, published two independent phase I clinical trial results at the same time Through DNA and RNA sequencing of tumor cells, we searched for new antigens specifically expressed by tumor cells due to gene mutation, and then constructed personalized tumor vaccine, which was delivered back to the body to activate immune cells and kill tumor cells with the above antigens This is the first successful cancer vaccine research in clinical trials A vaccine has long been expected to help the immune system recognize and eradicate cancer At present, it seems that the new antigen is an ideal target for tumor immunotherapy Because new antigens are only expressed specifically in tumors, it is almost impossible to induce tolerance and damage normal tissue cells According to cbinsights in a recent report, the new antigen vaccine is very different from those previously failed tumor vaccines It is a highly "personalized" vaccine, which has been regarded as the next major breakthrough in cancer treatment Here is the main content of the report compiled by the arterial network for you: first, what is the new antigen? 2、 The new antigen vaccine brings more personalized cancer treatment drugs 2 How does the new antigen vaccine work? 3、 How is the research process? 4、 The company that develops new antigen vaccine 5, how does new antigen vaccine develop next? Immunotherapy has played a central role in the fight against cancer Some immunotherapies treat diseases by looking for antigens (usually proteins) on the surface of cancer cells Sometimes, normal cells also express some antigens, which, if destroyed in large quantities, will pose a great threat to health As a result, researchers are increasingly using the new antigen vaccine as a cancer treatment What is the new antigen? New antigens are protein fragments found only in cancer cells Because of their unique nature, targeting them allows the patient's immune system to detect and attack cancer cells rather than healthy cells Since 2015, when the new antigen vaccine was first used in human clinical trials, there has been increasing interest in this field Changes in interest in new antigens (source: cbinsights) cancer cells are hard to track because they have the magical ability to constantly adapt to different environments The new antigens provide a new and complex way to track these cancer cells Although this is still a new area of research and only early data are available, we can already see existing enterprises and start-ups investing in this area Next, we will study the working principle of new antigen vaccine and why this technology may be the key to cure cancer It's tricky for the new antigen vaccine to bring more personalized drug cancer, because the rapid growth of abnormal cells can often bypass many defense mechanisms and not be found by the immune system In addition, antigens are often expressed in normal cells and cancer cells, making the body vulnerable to low immunity This provides an opportunity for the intervention of new antigens New antigens are cancer specific mutations that can be thought of as radio antennas on the surface of cancer cells Our goal is to find these antennas and trigger white blood cells called T cells to attack cancer cells Because only cancer cells express new antigens, these new antigens are ideal targets for the immune system to attack without damaging normal cells If researchers can predict which antigens are present in a patient's tumor, they can enable the immune system to track them There are two subtypes of new antigens in the general cancer immune cycle (picture source: cbinsights): shared new antigens, which are not specific to individuals or tumor types Two different people may also have the same new antigens Personalized new antigen has high specificity for individual tumor Because of the high mutation rate of some cancers, more new antigens are produced But this is actually desirable, because more new antigens mean more immune systems are tracking targets This occurs in cancers such as melanoma (skin cancer) and lung cancer, which is why new clinical trials to explore new antigen vaccines are targeting these cancers In fact, since 2015, three key clinical trials using the new antigen vaccine have targeted melanoma New antigen vaccine delivery platform vaccines are usually composed of weakened or dead cells they are trying to attack, and researchers are seeking to develop personalized vaccines based on new antigens The vaccine can be injected into patients to help stimulate the immune response In addition to selecting new antigens that produce the strongest immune response, researchers are currently working to assess which new antigen delivery platforms are most effective Because of the different biological characteristics of each vaccine, each vaccine platform has its own advantages and disadvantages, but they all try to use the new anti-tumor to induce anti-tumor response The following are the main vaccine platforms for the study of new antigen vaccines Several early clinical trials based on these platforms are in progress Synthetic long peptide (SLP): peptide vaccine is the most commonly used vaccine in clinical trials It can call two types of T cells (the body's defense cells) at the same time to trigger an immune response However, unlike other platforms, SLP vaccines require an additional component in the vaccine, adjuvant Adjuvants must be used with new antigens in order for the vaccine to work properly and activate the immune response RNA vaccine: RNA molecules that produce new antigen polypeptides can also be used as vaccine platforms targeting cancer cells RNA vaccines do not need additional adjuvants to stimulate the immune response, because it is the genetic material of many pathogens, and our immune system has been alert to these pathogen molecules However, the development of this vaccine platform is relatively difficult Dendritic cell vaccine: as antigen presenting cells (APCs), dendritic cells play an important role in human immune system They process antigens and present them on the cell surface, then stimulate T cell response It has two disadvantages: high cost and labor-intensive manufacturing process Viral or bacterial based delivery platforms are also used to carry new antigens in these vaccines A bacterium called Listeria monocytogenes has become a potential choice How does the new antigen vaccine work? Most researchers use computer simulation methods, which use algorithms to predict which new antigens will make the immune system work most effectively according to the tumor characteristics of patients Instead, some people choose in vitro methods to extract tumor cells and conduct experiments to determine which new antigens produce which effects New antigen vaccines are individualized according to the specific tumor conditions of patients Although there are some differences in the development of these vaccines by different companies, there are also general steps in the manufacture of new antigen vaccines: 1 Biopsy of tumors Tumor samples were taken from patients for further laboratory tests This enables researchers to make more detailed inferences about the outline of the tumor; 2 Sequencing and computational analysis The researchers sequenced the exons of tumor cells and normal cells, the parts of the genome that ultimately produce proteins This enables researchers to find unique mutations in tumor cells, such as inserting or deleting additional DNA base pairs; 3 Predicting and selecting specific new antigens as targets This step involves identifying the patient's specific tumor mutation, the new antigen These new antigens are more likely to cause the immune system response and attract T cells to attack cancer cells Some companies are developing their data and prediction algorithms to achieve higher accuracy; 4 Developing personalized vaccines Based on the prediction of the new antigen can stimulate the immune system to attack cancer cells, using the delivery vector (such as peptide, RNA, etc.) to design personalized vaccine; 5, injection of new antigen vaccine After the vaccine has been developed, it is injected to patients Source: cbinsights checkpoint inhibitors can improve the efficiency of new antigen vaccines Some companies combine the vaccine with another immunotherapy, checkpoint inhibitors, to strengthen the immune system's attack on cancer cells that may still escape Normally, the immune system uses T cells to track down foreign pathogens, such as bacteria or viruses, and then deploy other immune cells to attack But cancer cells are unique in their ability to avoid detection by immune cells In fact, cancer cells can hide behind the "shield" on the cell surface and cheat T cells This allows cancer cells to fuse with normal cells to avoid triggering immune attacks This is where checkpoint inhibitors work It can prevent cancer cells from "deceiving" T cells and make them recognize and attack cancer cells correctly Image source: cbinsights checkpoint inhibitors are core immunotherapy categories, usually administered intravenously, and approved drugs have been on the market since 2011 This therapy combined with the new antigen vaccine can achieve higher efficiency of cancer cell eradication How is the research process? Compared with experienced therapies such as checkpoint inhibitors, the new antigen vaccine is still very new in the field of cancer immunotherapy Although the relationship between immune system and new antigens has been proved in the beginning of this century, human research is just in its infancy In 2015, the results of the first human clinical trial using the new antigen vaccine were published Three melanoma patients were enrolled in the study, each receiving a dendritic cell-based vaccine The results showed that the release of these new antigens stimulated the production of more T cells This suggests that the vaccine can alert the immune system to respond to cancer cells that need to be attacked In 2017, two other studies published test results on the effectiveness of new antigen vaccines in humans NIR Hacohen and Catherine Wu, two co founders of neon therapeutics, helped with one of the studies In this study, six patients with melanoma were vaccinated with a peptide based new antigen vaccine consisting of up to 20 new antigens Within 2.5 years, four of them recovered from cancer The remaining two patients recovered after receiving additional treatment with checkpoint inhibitors The research design is shown in the following figure: Source: cbinsights in another 2017 study, Ugur Sahin, researcher of Johannes Gutenberg University of Mainz in Germany, founder and CEO of cancer treatment company biontech, developed vaccines using RNA molecules, each containing 10 new antigen mixtures The vaccines were used in 13 patients with melanoma Within 12-23 months, eight patients got rid of cancer, and one patient got better after receiving checkpoint inhibitor treatment As mentioned above, melanoma is the key target of these three clinical trials Because of its high mutation rate, new antigens are more likely to attack cancer Pharmaceutical companies that make new antigen vaccines are using different technologies and platforms to develop their own proprietary new antigen vaccines Next, let's look at the major players in the field and what they have achieved Biontech Germany's biontech company is a key player in the field of new antigen vaccines