Immunotherapy for cancer: Is it reliable?
February 27, 2017 Source: People's Daily
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Speaking of immunotherapy, some people first think of the Wei Zexi incident last year. This incident once made the immunotherapy controversial, and even many people posted the label of "deceptive". So, what exactly is immunotherapy? Is it difficult to use it to treat tumors? What is the latest progress at home and abroad? What is the future prospect? The reporter interviewed the authoritative experts in the industry on relevant issues--Dr. Chen Chen, Dean of Tsinghua University School of Medicine, Director of Institute of Immunology, and Dr. Li Kang, senior drug research and development scientist of Baekje Shenzhou Biotechnology Co., Ltd., trying to present immunotherapy. The whole picture.
What is immunotherapy?
Through various means, regulate and activate the body's immune system to treat diseases
To understand immunotherapy, the first thing to do is to figure out what the immune system is. The body's immune system is mainly composed of immune organs (bone marrow, spleen, lymph nodes, tonsils, etc.), immune cells (lymphocytes, mononuclear phagocytes, platelets, etc.) and immune molecules (complement, immunoglobulin, interferon, interleukin, etc.). )composition. The immune system is the most important "defense system" of the human body. It can identify and eliminate foreign invading pathogens, mutant tumor cells, aging cells and dead cells in the body, and maintain its own stability.
The immune system is able to withstand many diseases, but it often seems powerless when faced with tumors. Why?
According to experts, cancer is derived from one cell. The transition from a normal cell to a tumor cell goes through a multi-stage process, usually from precancerous lesions to malignant tumors. Why does the immune system "open the side of the tumor cells"? This is because the tumor cells are also mostly derived from the human body. The immune system often mistakes them as "self-persons" and does not actively attack. In addition, tumor cells will try to escape "monitoring." For example, in order to prevent "mis-injury" of normal cells in the body, the immune system has its own "brake system", and the tumor cells of "狡猾" will quietly step on this "brake" to paralyze the immune system.
Immunotherapy is a method of treating diseases by regulating and activating the body's immune system through various means. The treatment of tumors is the most important application field of immunotherapy.
According to data released by the World Health Organization, 8.8 million people die of cancer every year in the world, and they are growing rapidly. Scientists around the world are also working on various anti-cancer therapies. In recent years, immunotherapy has become the focus of cancer treatment, and a series of breakthrough results have emerged. In 2013, the US Science magazine selected tumor immunotherapy as the biggest scientific breakthrough in the year. In 2015, it also listed tumor immunotherapy as one of the four scientific advances worthy of attention.
How does immunotherapy work?
Or "tell" the characteristics of tumor cells, or stop the tumor cells from giving the immune system "brakes"
So how does immunotherapy work specifically? What role did it play?
"'狡猾''s tumor cells rely on 'camouflage' themselves and suppress the immune system. In contrast, immunotherapy starts from these two aspects to deal with cancer." Dong Chen said that immunotherapy is the characteristics of tumor cells. "Tell" immune cells, let the immune system recognize and kill them, and second, prevent tumor cells from giving the immune system "brakes" and release their inhibitory function. A typical application of the former is CAR-T (chimeric antigen receptor T cell) therapy, and the latter is represented by an immunological checkpoint inhibitor such as PD-1 (programmed cell death 1) antibody drug.
In the immune system, T lymphocytes are the "main force" against cancer. Early studies have found that interleukin 2, an active component of the immune system, promotes the growth of T cells and fights tumors through T cell proliferation. Later, the researchers envisioned: Why not directly culture immune cells in vitro and then return them to the body to destroy tumor cells? Therefore, the immune cell adoptive return technology came into being. From LAK (lymphokine-activated killer cell) therapy, CIK (cytokine-induced killer cell) therapy, adoptive T cell therapy, and the latest CAR-T cell therapy are all of this type of technology.
However, an important question that was not solved by early LAK cell therapy and CIK cell therapy was how to make these "foreign aid" immune cells recognize tumor cells? CAR-T therapy addresses this problem. In the process of in vitro culture of immune cells, genetically modified methods allow T cells to express specific tumor antigen receptors, which is equivalent to "telling" the characteristics of tumors. T cells are equipped with "navigation" to help them find tumor cells.
Explained in more general terms, CAR-T therapy can be compared to the injection of a cancer vaccine into the human body. After extensive proliferation in vitro, these engineered T cells are injected back into the patient to attack cancer cells expressing these antigens. "Many T cells in tumor tissues are directed against tumors. These T cells are returned to the patient and have a better therapeutic effect." Dong Chen said, "Now this technology is in the ascendant and has a significant effect in the treatment of leukemia. "
In 2015, only 1 year old British baby girl Laila Richards received CAR-T cell therapy. She had very severe leukemia. After all other treatments failed, the doctor injected 50 million genetically modified T cells to track and kill cancer cells in her body. In the end, Leila's leukemia "disappeared." Although it is too early to conclude that Laila is completely cured, doctors believe that her recovery is a miracle in itself. In another study, organized by the American Anderson Cancer Center, more than 50% of patients with melanoma responded with adoptive T-cell therapy.
Of course, the current CAR-T cell therapy is not too optimistic, there is still a long way to go. There are two key points in whether this therapy can make great progress. One is to break through the problem of not finding a tumor-specific target for decades, and the other is to improve safety and control immune overreaction.
Correct treatment of immunotherapy
Can't equate DC-CIK therapy with immunotherapy, and therefore negate the entire immunotherapy
The second typical application of immunotherapy is to prevent tumor cells from "brake-off" to the immune system, which is achieved by immunological checkpoint inhibitors. The representative drug is PD-1 (programmed cell death 1) antibody drug. Currently, the US Food and Drug Administration has formally approved several PD-1 monoclonal antibodies for the treatment of three advanced tumors with drug resistance and malignant metastasis: melanoma, non-small cell lung cancer (about 80% of lung cancer) and kidney cancer.
How to understand the "brake system" of immune cells? Experts explain that the important function of CD8 T cells in the immune system is to identify cells that may be harmful to the body. But it repeatedly repeats complex procedural "confirmation" during the start and attack to ensure that the cells killed are cancer cells rather than healthy cells. In short, the activated CD8 T cells also express a set of protein molecules that can receive external signals and self-inhibition. Immunologists refer to these proteins as "immunoassay suppression receptors".
"PD-1 is the most important immunosuppressive receptor inhibitor known at present." Li Kang said. PD-1 mAb is a bioprotein drug against PD-1. It specifically binds to the PD-1 receptor and blocks its reception of signals from PD-L1 (programmed cell death receptor-ligand 1). Li Kang said: "A CD8 T cell can kill several cancer cells in succession. Some CD8 T cells with memory function can survive for a long time, once again encounter cancer cells, and can immediately enter the activation state."
The most well-known case of treating melanoma with PD-1 antibody is the treatment of former US President Jimmy Carter. After radiotherapy of four tumor lesions in Carter's brain and removal of 10% of liver tissue and removal of liver lesions, the doctor continued immunotherapy with PD-1 antibody. In March 2016, the medical team announced that cancer cells could no longer be found.
Li Kang believes that PD-1 mAb has occupied a major position in the treatment of these three advanced malignancies. It is expected that as PD-1 monoclonal antibody is further expanded and advanced in clinical trials, it will be applied to more tumor treatments.
Also worthy of attention is the "combination boxing" of antibody combination. Among the immunological checkpoint inhibitors, the previously discovered CTLA4 (cytotoxic T cell antigen 4) antibody also has a similar function. "The combination of CTLA4 and PD-1 antibodies is far superior to single antibody in terms of melanoma treatment response and multi-year survival rate," said Dong Chen.
However, experts also said that "it is a three-point drug", and the side effects of PD-1 monoclonal antibody include pneumonia, enteritis, and thyroid dysfunction.
"There are some controversies about immunotherapy, mainly because some people have misunderstood the concept." Dong Chen said that the DC-CIK therapy used in the Wei Zexi incident is a kind of early immunotherapy because the clinical trials are not effective enough. There is no large-scale promotion abroad. "It is neither accurate nor irresponsible to equate DC-CIK therapy with immunotherapy." Experts believe that it is not a blind eye, because the DC-CIK therapy does not work well and negates the entire immunotherapy.
"Immune therapy has seen the dawn." Dong Chen said, "In some melanoma and lymphoma patients, immunotherapy has shown good results, and like vaccination, it can produce a lifelong protection mechanism. Immunotherapy may It is an important weapon for mankind to overcome cancer in the future."
Extended reading
How to expand the scope of treatment and how to reduce "toxicity"
Immunotherapy meets the challenge
Dong Chen, dean of Tsinghua University School of Medicine and director of the Institute of Immunology, believes that immunotherapy may be an important weapon for humans to overcome tumors in the future, but it also faces several challenges: First, expand the scope of treatment. At present, cell therapy is only effective for certain cancers such as lymphoma and blood cancer, and it is not effective for solid tumors. Although PD-1 therapy has been conceptually verified, how to improve the effect and expand the beneficiary population still needs further research. The second is how to reduce the "toxicity" of immunotherapy and improve the quality of life of patients. The side effects of some treatment techniques are still large, such as CTLA4, the side effects are still very strong. Third, the research of immunotherapy still needs a process.
"In fact, there are many 'brakes' in the immune system, and there are extracellular cells inside and outside. There are also network relationships between different immune cells. How to find new breakthroughs, there is still a long way to go." Say.
To treat cancer, a "can" that cannot be avoided is clinical research. “In the end, I have to go to the clinic to verify.†Dong Chen believes that “in terms of domestic research, clinical research is still relatively weak.†Many large pharmaceutical companies are reluctant to go to China for clinical trials, on the one hand, lack of regulation. The more important reason for the clinical trial base is the lack of "physician scientists" who can master new knowledge and therapy, and can do both scientific research and medical treatment. Dong Chen believes that the new therapy requires a relatively complete clinical trial program, and the possible side effects need to be estimated and prevented. It must be based on the “science foundationâ€.
“Another aspect of the scientific roots is basic research. In particular, basic research and translational research conducted through patient samples.†Dong Chen said, “It is necessary to combine several aspects. Immunotherapy is also a systematic project, besides being solid. Doing a good job in research on the ground is also inseparable from the efforts of all sectors of society."
At present, immunotherapy has been recognized as a “fourth treatment†after surgery, radiotherapy and chemotherapy. Some experts have suggested that with the good results of immunotherapy, it may not be used as a supplementary treatment method. Some patients may have appropriate intervention timing, and multiple treatment methods should be combined. As people's understanding of tumors deepens, precision medical methods represented by gene sequencing will also promote the development of immunotherapy.
Li Kang, a senior drug research and development scientist at Baekje Shenzhou Biotechnology Co., Ltd., believes that human understanding of the autoimmune system and tumor immunotherapy is still only the tip of the iceberg. From a comprehensive understanding of the immune system, there is still a long way to go to the correct use of tumor immunotherapy drugs and methods. In daily life, paying attention to maintaining physical function and keeping the immune system in an optimal state is an important basis for tumor immunotherapy. (Guye Kai finishing)
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