In 1890, a New York orthopedic physician named William Corey saw a woman who had just turned 17 with an advanced malignant sarcoma on her arm. Corey amputated the patient's right arm as standard at the time, but the cancer spread throughout the patient's body, and she died shortly after the operation. This incident gave Corey a lot of stimulation, and he was determined to find a cure for the sarcoma. He soon found a successful case where the patient had lived 7 years without relapse. He studied the case carefully and found that the patient had contracted erysipelas during his treatment. It's a skin infection caused by an invading bacteria that causes the patient's skin to become red, painful, and often accompanied by a high fever. The case showed that just after a high fever, the patient's tumor shrank rapidly, and finally disappeared completely. Corey wondered if erysipelas activated the patient's immune system, and the active immune cells "smoothly" killed the cancer cells?
In order to verify his idea, Corey went to the library to check the information and found that similar cases had indeed occurred before, and the patients' tumors had shrunk rapidly after a high fever. So he figured out a way to convince a cancer patient to get a strep shot, which worked surprisingly well. Next, Corey used this method to treat 10 cancer patients. Although they all had varying degrees of remission, two of them died because of the infection. So Corey decided to use bacterial toxins extracted from bacteria instead of live bacteria. Experiments have shown that this method can also cause high fever, but it will not let the patient get infectious diseases.
After experimenting with several bacterial toxins, Corey found the perfect combination and named it Corey Toxin. This is the first time humans have tried to use the immune system to deal with cancer, which was considered a revolutionary innovation back then. Unfortunately, follow-up tests have shown that the effectiveness of Cory's toxin is not high, but the risk is very high. As a result, this method was quickly replaced by chemotherapy and radiation therapy. However, both chemotherapy and radiotherapy belong to the anti-cancer therapy of "killing a thousand enemies and destroying eight hundred", and the side effects are too great. Therefore, scientists have developed targeted targeting according to the special properties of different cancer cells. Drugs that drastically reduce the side effects of treatment. However, although most of the existing targeted drugs are highly targeted, their universality is generally not good, resulting in their high prices. Many cancer patients have gone bankrupt because of this, so targeted therapy still cannot be regarded as anti-cancer. Ideal solution.
So, some people think of immunotherapy again. In fact, healthy people don't get cancer, not because they don't have cancer cells in their bodies, but because the immune system kills all the newly generated cancer cells. Cancer cells in cancer patients have evolved a special way to suppress the activity of the immune system, which allows them to metastasize. In the 1990s, scientists found several ways to reactivate the immune system, and on this basis developed a series of anti-cancer drugs based on the immune system, which are the famous PD1 and PD-L.
However, when it comes to the immune system, the first thing most people think of is not PD1, but vaccines. The new crown epidemic has taught everyone the power of vaccines. Many scientists even believe that only the popularization of vaccines can make mankind completely out of the new crown epidemic.
Since vaccines are so powerful, is it possible to use them against cancer? The answer is yes. In fact, there are already HPV vaccines on the market that can prevent cervical cancer, and the effect is very good. But the vaccine, which targets a specific type of human papillomavirus, is limited in scope. Is it possible to develop a broad-spectrum anti-cancer vaccine that directly targets cancer cells? At least in principle, this possibility exists.
The April 8, 2022, issue of Science published a review article on the history and current status of cancer vaccines. It turned out that as early as the early 1990s, some people tried to use tumor antigens to make anti-cancer vaccines, but unfortunately the results were not good. The main reason is that although this antigen has a high probability of appearing on the surface of tumor cells, there is also a small amount on the surface of healthy cells, and the immune system often chooses to ignore it, resulting in the inability of the vaccine to induce a strong immune response.
The solution to this problem is to switch to using neoantigens to make cancer vaccines. This antigen is only present on the surface of cancer cells and cannot be found on healthy cells, which greatly increases the specificity of the vaccine and the effect is much better. The problem is that the number of cancer neoantigens that have been discovered so far is not enough, and the specificity of the antigen itself is too strong. Each cancer has its own unique neoantigen, which is a bit like anti-cancer targeted drugs, although It is easy to use but the scope of application is too narrow and the cost is too high.
A second reason for the ineffectiveness of early cancer vaccines is that the antigens are not strong enough. Because of the limited level of technology at the time, scientists could only use antigen proteins to make vaccines. This vaccine can only activate immune B cells to make antibodies, but cannot mobilize more lethal immune T cells to fight, which requires antigen presentation. Cells help it. Antigen-presenting cells act as scouts, constantly synthesizing new antigens and presenting them to immune T cells, providing them with targets to attack.
The third reason for the poor efficacy of early anti-cancer vaccines is related to the treatment of cancer. Because cancer patients inevitably need chemotherapy and the function of the immune system is suppressed, it is easy to cause the vaccine to fail. For example, the only approved vaccine for advanced prostate cancer so far can only prolong the life of patients by 4 months on average, which is obviously not enough. So some scientists tend to think that anti-cancer vaccines are more suitable for prevention rather than treatment, but this requires vaccine manufacturers to be able to adjust the target of the vaccine at any time according to newly discovered neoantigens, which was difficult to achieve 30 years ago. To solve the above three problems, the best way is to develop a new nucleic acid-based vaccine. The vaccine itself is not an antigen, but a drawing that directs somatic cells to synthesize antigens. People who receive this vaccine will continuously produce new antigenic proteins in their bodies, which stimulates the immune system to a much higher degree than traditional antigenic vaccines.
This new nucleic acid-based vaccine includes DNA vaccines and mRNA vaccines, and the new crown epidemic has given mRNA vaccines a good opportunity to perform. The latter has proved through its own performance that this technology is at least safe enough, and the effect has reached designer's expectations. The biggest advantage of mRNA vaccines is that the design is simple. Scientists can quickly change the antigen sequence according to the actual situation, and then introduce the changed mRNA fragments into antigen-presenting cells, instructing them to continuously produce corresponding neoantigens to help immunity. T cells kill budding cancer cells.
This technical route is not complicated to say, and the success of the new crown vaccine has given scientists great confidence, so many countries have regarded anti-cancer vaccines as the next potential stock and invested huge amounts of research and development funds. However, this vaccine is too special, and clinical trials are quite difficult. Currently, it can only be tested in cancer survivors and those special populations born with a strong oncogene, and it is unlikely to be successful in the short term. But preliminary studies have shown that this vaccine can indeed stimulate a strong anti-cancer immune response, and the future is quite promising.
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