How many cancers can one cancer vaccine prevent?
arts/
Even with such advanced modern medicine, cancer, as abnormal cell proliferation caused by gene mutation, is still one of the major causes of death in the world, and it is also a major public health problem seriously endangering human health. According to the World Health Organization, it is estimated that there will be about 135 million cancer patients worldwide in 2020. Asia accounts for about 48.4% of the world's new cancer patients, and the number of cancer patients in China in 2020 will exceed 32 million.
The prevention and treatment of cancer is still the focus and difficulty of the current medical field. Among them, with the development of biology and medicine, people's understanding of cancer and their own immune system has deepened, and scientists have also realized that the immune system is the most lethal weapon against cancer. In recent years, the rise of cancer immunotherapy has also led more and more research teams to focus on cancer vaccines.
Cancer vaccine a major breakthrough
The mechanism of action of vaccines is actually the principle of immunity. A vaccine is a modified virus or a component of a virus. After the human body is vaccinated by oral or injection, an immune response will occur. When the human body encounters a real virus attack in the future, the trained immune system can quickly respond to protect the body from the virus. The same goes for cancer vaccines.
More than 20 years ago, cancer vaccines were hailed as a major breakthrough in the treatment of cancer. Specifically, cancer vaccine is a therapeutic and preventive immunotherapy strategy that activates the human immune system by targeting tumor cell-associated antigens and exerts specific anti-tumor effects. Cancer vaccines identify proteins present on specific cancer cells that can stop cancer cells from growing, prevent cancer from recurring, and remove cancer cells that remain after treatment.
The basis of cancer vaccinology is to awaken the immune system to the existence of cancer by providing antigens associated with tumor cells to the immune system. Once the immune system is awakened, it is not only able to continuously search for similar suspicious cells throughout the body, but also retains memory of abnormal antigens so that it can attack again quickly if the tumor recurs.
Currently, some well-known cancer vaccines are preventive vaccines, such as the human papillomavirus (HPV) vaccine for cervical cancer. However, to a certain extent, the HPV vaccine is also a virus vaccine, because the relationship between HPV virus and cervical cancer is very close, and the vaccine has a very good preventive effect on the virus, which also prevents cancer caused by the virus.
As for the cancer therapeutic vaccine, the world's first and currently the only one approved by the U.S. Food and Drug Administration (FDA) is Provenge for prostate cancer. However, the effect of the Provenge vaccine is limited, and the average survival time of patients after vaccination is only prolonged. 4 months.
In addition, Provenge's high price and complicated treatment plans have also discouraged many doctors and patients. Provenge's sales in 2011 were only 214 million US dollars, which was much different from the 350-400 million that Haikou boasted. By 2014, Dendreon, the developer of Provenge, was declared bankrupt due to its inability to repay huge debts, and its fate was woeful.
There are still dozens of various cancer vaccines in clinical trials in the United States. Similar to Provenge, they all use a certain cancer cell analog to elicit an immune response and immune memory. However, it is important to point out that most clinical trials of therapeutic cancer vaccines have yielded unsatisfactory results. A large part of the reason lies in the diversity of cancer cell antigens and tumor immune escape mechanisms.
From the perspective of antigenic diversity, although some proteins that are abnormally highly expressed by cancer cells are very good vaccine targets, like prostate cancer cells usually overexpress prostatic acid phosphatase, the vaccine developed based on this also mainly relies on major histocompatibility The complex presents antigen proteins to T cells, which is like finding viral antigens in a targeted manner, but each tumor patient's ability to present antigens and immune activation is very unique, which is the basis for most therapeutic cancer vaccines. Clinical trials add to the difficulty.
From the perspective of tumor immune escape, under normal circumstances, immune T cells in the human body can monitor and remove tumor cells. However, tumor cells can evade detection by the immune system by disguising themselves . Among them, there is a type of protein called PD-L1 on the surface of many types of cancer cells. When PD-L1 on the surface of tumor cells is combined with PD-1 on the surface of immune T cells, T cells will reduce proliferation or lose activity, thereby losing With the ability to recognize and fight tumor cells, tumor cells are able to evade attack by the immune system.
Over the years, the understanding of the mechanisms of immune evasion in cancer cells has also led to the development of a variety of tools for cancer immunotherapy, including antibodies, peptides, proteins, nucleic acids, and immunocompetent cells. The application of these technologies to cancer vaccines can be divided into three categories - tumor or immune cell vaccines, protein/peptide vaccines, and nucleic acid vaccines (DNA, RNA or viral vectors).
Most cancer vaccines are protein/peptide vaccines that target peptide antigens to induce immunity against specific epitopes derived from vaccinated proteins/peptides expressed in cancer cells. However, such cancer vaccines often require individual design due to the enormous interindividual diversity of major histocompatibility complex (MHC) molecules that present peptides to T cells. In addition, tumor cells often evade T cell-mediated immunity by interfering with mechanisms of peptide presentation, rendering protein/peptide vaccines ineffective.
Based on the diversity of cancer cell antigens and tumor immune escape mechanisms, it is difficult enough to personalize cancer vaccines, and a universal therapeutic cancer vaccine is still far away.
universal cancer vaccine
Obviously, in the case of cancer, the development of a universal therapeutic cancer vaccine may profoundly change the current landscape of cancer treatment. On May 25 this year, the research team of the Dana-Farber Cancer Institute in the United States published a research paper in the top international academic journal Nature.
In this study, the researchers developed a novel cancer vaccine that overcomes individual differences in cancer immunity by targeting MICA/MICB stress molecules to activate two main types of immune cells - T cells and NK cells, Causes a coordinated all-out attack independent of tumor antigens. Preliminary results demonstrate the efficacy and safety of the cancer vaccine in mice and rhesus monkeys.
The first thing to know is that, in general, cancer immunotherapy works by stimulating the activation of T cells, making them more effective against cancer. At the same time, more NK cells also play a minor role in this therapy. However, NK cells are usually difficult to fight against cunning tumor cells. Originally, NK cells can attack them by recognizing stress proteins expressed on the surface of tumor cells, but tumor cells shed proteins to avoid being monitored by the immune system . In other words, one of the reasons the immune system struggles to recognize tumors is that tumor cells prefer to strip off specific proteins on their surface that the host's immune system can recognize.
Unlike past vaccine designs, in this latest study, Kai Wucherpfennig's group targeted the vaccine against two surface proteins, MICA and MICB, which activate ligands for T cells and natural killer (NK) cells, accelerating the The immune system destroys the tumor. Among them, MICA/MICB is a kind of cell stress molecule, and its expression is very low in normal tissues, but its expression is significantly up-regulated in various tumor cells.
Studies have shown that MICA/MICB can bind to the NKG2D receptor on the surface of T cells and NK cells and be recognized by effector cells, mediating the killing effect on tumor cells. Based on this, the MICB-vax vaccine designed by Kai W. Wucherpfennig's laboratory can disrupt this cleavage process by increasing the density of proteins on the surface of tumor cells, which the researchers also call "stimulating protective immunity."
The researchers have now conducted vaccination experiments in MICB transgenic mice, similar to human cancer cells. The study showed that vaccinated mice inhibited MICB shedding to undetectable levels and significantly increased the cell surface protein density of MICB in melanoma cells, and the vaccine showed significant control over melanoma cells and lymphoma cells expressing MICB or MICA. effect.
To assess vaccine-induced immune memory, the researchers injected mice with melanoma virus 4 months after the initial immunization and found that the mice were completely protected.
In addition, the researchers tested the prevention of metastatic and recurrent tumorigenesis by immunizing mice after surgical removal of the primary tumor using two models of spontaneous metastasis, a melanoma model and a triple-negative breast cancer. models and vaccinate them. After a series of experiments, the researchers found that the mice had significantly less cancer metastasis after the vaccination.
The study showed that the vaccine significantly reduced the number of lung metastases detected in both models more than 1 month after surgery, and histological analysis of lung sections further showed that the vaccine resulted in a significant reduction in the number and size of metastases compared to the control group. Since the expression of MICA/MICB is a common feature of tumor cells, vaccines targeting this target are broad-spectrum, eliminating the need to customize individual vaccines for each patient .
Likewise, the researchers also tested the vaccine for safety and immunogenicity in the non-human primate rhesus monkey. The study showed that all four rhesus monkeys developed anti-MICA and anti-MICB antibodies after immunization, and with subsequent booster immunization, the titers increased 100-1000-fold, and no clinical side effects were found after immunization, which is the safety of the vaccine Sex provides prima facie evidence.
Although further clinical trials are needed to evaluate the potential of this cancer vaccine in humans for a universal cancer vaccine, this is still a major advance in therapeutic cancer vaccines.
Facing the Confidence of Cancer
In the past many years, people have "smell cancer", but today, the update of technology has given people more options to face cancer. In fact, as early as 2006, the World Health Organization (WHO) officially announced that cancer was included in the category of chronic diseases.
From the perspective of cancer treatment, as early as 1981, the World Health Organization proposed that cancer is a chronic disease, of which 1/3 can be prevented, 1/3 can be cured through early detection, early diagnosis, and early treatment, and 1/3 can not be cured. Cure, but with appropriate treatment, it can be controlled and a better quality of life can be obtained, thereby prolonging survival.
In terms of curability, it takes at least 3 years from the appearance of cancer cells to the growth of a 1cm-diameter cancer mass. The slow growth process allows people enough time to achieve "early detection, early diagnosis, and early treatment", which is also a cancer of secondary prevention. According to 2014 American Cancer Society (ACS) statistics on cancer, cancer mortality has steadily declined, with an overall drop of 20 percent.
For the remaining 1/3 of advanced cancer patients, although incurable, with several major advances in medical treatment and the emergence of more and more anti-cancer methods such as chemotherapy, targeted therapy, and immunotherapy, the survival of cancer patients has been greatly improved. rate has been greatly improved. For example, the five-year survival rate for patients with chronic myeloid leukemia has increased by 90% from 30% 15 years ago. As long as the medication is taken on time, the patient's survival can be extended by nearly 20 years.
As mentioned above, one-third of cancers are preventable as a chronic disease - more than 30% of cancers could be avoided through healthy lifestyle changes such as not smoking tobacco, eating a healthy diet, maintaining physical activity and strictly limiting alcohol consumption. However, while science and technology provide a more efficient and convenient way of life, it also makes people's lives more irregular and uncontrolled.
The World Cancer Report 2014 pointed out: "Although the medical community has clearly identified many risk factors for cancer for a long time, such as smoking, alcohol abuse, unhealthy diet, obesity, lack of exercise, etc., these problems are in the low to medium level. Income countries still exist. In contrast, developed countries have seen dramatic declines in cancer incidence and mortality in recent years due to active promotion of healthy lifestyles.”
From the perspective of coexistence with cancer, in fact, the four chronic diseases with the highest mortality rate in the world: the top two are cancer (28.1%) and cardiovascular and cerebrovascular diseases (27.1%). It is not difficult to see that the mortality rate of cardiovascular disease is comparable to that of cancer. However, most people take cardiovascular disease calmly, but facing cancer is like a death sentence. The fear of cancer far exceeds that of other diseases such as cardiovascular disease. The root of the fear is the public's "unknown and misunderstood" cancer.
From "talking about the discoloration of cancer" to "coexisting with cancer", from being helpless in the face of cancer to the development of today's universal cancer vaccine, people have more confidence.