Immunotherapy: let the tumors unload camouflage
March 08, 2018 Source: Science and Technology Daily
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At a meeting of the 13th National People's Congress held on March 5, Premier Li Keqiang pointed out that the national science and technology investment should be inclined to the people's livelihood, strengthen the prevention and control of major diseases such as cancer, and make science and technology better benefit the people. .
When it comes to conquering cancer, the most popular immunotherapy in the anti-cancer circle seems to open up another path for humans to deal with cancer. Since March 2016, former US President Carter announced that melanoma brain metastases have been cured by immunotherapy, and immunotherapy has been regarded as an anti-cancer "artifact." In the past 2017, there have been many exciting advances in immunotherapy research both at home and abroad. The United States has approved the listing of two CAR-T (a type of cellular immunotherapy) therapy. In China, many companies have proposed anti-PD. -1/PD-L1 monoclonal antibody (a type of immunotherapeutic drug) is applied for marketing, and process approval is underway...
At the beginning of February this year, the new issue of Science published a supplement to the theme of precision medicine and tumor immunotherapy in China. It published dozens of professional articles from experts in the field of precision medicine and tumor immunity, showing China's immunotherapy. Scientific research strength.
Immunotherapy has come to the end of the "old eight" and "three axes"
"In the past, doctors used tumors to treat 'tumor' and 'three-axes'." Gao Yong, director of the Department of Oncology, Oriental Hospital, Tongji University, said that "the old eight" refers to eight drugs such as doxorubicin, "three-axe" It refers to chemotherapy, radiotherapy, and surgical resection. "If the old eight and the three axes can't be dealt with, we will be poor."
Immunotherapy now offers a revolutionary technology to combat tumor cells. "Our own immune system is a very powerful monitoring system, and tumor cells have been trying to escape," Gao Yong said. Immunotherapy removes the "camouflage of the camouflage" of tumor cells by means of antibody injection or intracellular gene editing, and helps the immune system recognize the "enemies" and eliminate them accurately.
"In the two main aspects of immunotherapy, China has carried out a lot of research." Shen Lin, member of the Beijing CPPCC and vice president of Peking University Cancer Hospital, said, "For example, immunological checkpoint inhibitors, commonly known as anti-PD-1 /PD-L1 drug, listed in foreign countries for about two years, China's drug trial department has accepted the application of new drugs for domestic pharmaceutical companies; and in the field of cellular immunotherapy, such as CAR-T therapy, China has begun very early The most likely clinical research is done in China."
Shen Lin expects that in 2018, immunotherapy related products of several pharmaceutical companies in China will be launched, and indications for marketed products include non-small cell lung cancer, lymphoma and melanoma. “The clinical trial research of domestic enterprises in this area has been basically completed, and some products of multinational enterprises have also completed clinical trials in China.†Shen Lin said.
Prior to this, the way to receive immunotherapy in patients with advanced cancer in China is mostly to participate in clinical trials, or to go abroad for treatment. The number of clinical trials is very limited, and the treatment abroad is also expensive, and the urgent need urges relevant departments to urgently promote the review and approval process for new immunotherapy drugs.
According to the official website of the Drug Evaluation Center of the State Food and Drug Administration, February 8th: In order to further encourage innovation and meet the urgent clinical drug needs of patients with advanced cancer, the Center organized the anti-PD-1/PD-L1 monoclonal antibody application data requirements. The symposium will form the basic requirements for the data of the declared listing. This clear rule was interpreted by the industry as a "prelude" to the arrival of immunotherapy.
"Running with the world" to develop anticancer drugs suitable for China
"Unlike the cancer spectrum of Western countries, China needs its own cancer treatment drugs." Shen Lin said frankly that there is a gap between China's immunotherapy and foreign countries, but unlike the gap in innovative drug research and development, it is almost "running". status.
"Driver gene mutations are more" "Using Chinese medicine" "Hepatitis B virus carriers are more"... The characteristics of these Chinese people make China's cancer disease map have its own characteristics. "For example, in China, liver cancer is a high-grade tumor, which is caused by hepatitis B virus infection." Shen Lin said that in the treatment of primary liver cancer, China's previous treatment level always lags behind foreign countries, and currently China is developing immunotherapy for liver cancer. After the study, it has achieved very good prospects and has completed clinical research. Relevant drugs may be approved for marketing this year, and the therapeutic effect is expected to be consistent with international standards.
In the immunotherapy of gastric cancer with the strongest heterogeneity, "Our classification of diffuse gastric cancer was recently accepted by the journal Nature, and will be published in the near future." Shen Lin said that we found different treatments. The different responses of the population to immunotherapy, for research reasons, are the first to predict different responses to treatment by different populations through proteomics.
In the primary use of CAR-T treatment for non-solid tumors such as leukemia, CAR actually acts as a commander, guiding and commanding T cells to destroy cancer cells. "Extract the T cells from the patient's blood and put them on the 'CAR' by genetic modification. After a large number of amplifications and then return to the patient, they can kill the cancer cells." National "Thousand Talents Program" entrepreneurial talents, biologists Yang Guanghua introduced that CAR must be “sharp†and “temperateâ€, otherwise it will cause the human body's cytokine storm and endanger life. "On the one hand, we must identify specific gene antigenic sites in cancer cells, and on the other hand, we must be able to control the 'switch' by adding drugs to accurately kill cancer cells when necessary." In the link, Yang Guanghua team obtained the only patent for inducing lentiviral vector patents and cancer cell recognition targets in China. At present, animal experiments have been completed and clinical trials are being submitted.
Achieving the "People's Medicine" professional talent team needs to be expanded
Although the new drug has been approved as "a popular expectation," this does not mean that the victory of human and cancer war has been fixed.
In the courseware of Dr. Lu Zhihao, deputy director of Peking University Cancer Hospital, it can be seen that different tumor types are not sensitive to drug immunotherapy. "Most tumors, such as lung cancer, breast cancer, etc., are only 10% to 30% effective in immunotherapy. The overall effective rate of immunotherapy for gastrointestinal tumors in China is only about 17.1%." Lu Zhihao said.
In other words, even if the immunotherapeutic drugs are approved for “inclusiveâ€, it is not necessarily effective for all patients. "The body's immune system is very complex, and the factors affecting it are diverse. The difference in the efficacy of patients receiving the same treatment is also very large," Shen Lin said.
"Super-progress, false progress, and adverse reactions are all possible." Lu Zhihao explained that super-progress is that the tumor not only shrinks or disappears, but grows rapidly; the pseudo-progress is that the tumor initially increases and then shrinks; Immunotherapy-related adverse reactions are completely different from conventional chemotherapy and targeted therapy, and are the result of the human immune system attacking its normal tissues and organs.
If there is super progress, the patient's survival time is generally only 2-4 months, which makes the "pre-judgment" subject urgent and significant. Lu Zhihao said that patients often come to the hospital to ask for immunotherapy. Due to the excessive aura of immunotherapy, patients often ignore it as “picking people.†It is very dangerous to pick the wrong one.
At present, the research of scientists is precisely looking for the basis of "picking people" and doing "putting drugs on people." This basis includes biomarkers and the like. In May 2017, the US Food and Drug Administration (FDA) approved the first biomarker to differentiate anti-tumor therapies. "China will soon start clinical research in this area. I believe that next year or the end of this year will get the desired results." Shen Lin said.
At the same time, the “Puzhong†of immunotherapy has put forward higher requirements for medical workers. If the “clinical research†stage before the new drug is not listed is the scientific level of the medical elite, then the test will test China. The entire medical worker community.
“You may be able to inject immunotherapeutics in the county hospital, but the subsequent evaluation of the efficacy, adjustment of the program and monitoring and management of adverse reactions require special professional knowledge.†Lu Zhihao expressed concern about the reserve of resources for immunotherapy Insufficient, may make it difficult for patients to get the desired effect.
“There is a large amount of personnel training and professional participation.†As a member of the Beijing Municipal Committee of the Chinese People's Political Consultative Conference, Shen Lin proposed that the oncology specialist training program should be optimized so that more oncologists can reach a level of homogeneity and patients can be in different medical institutions. Can enjoy the same quality of cancer treatment services. (Reporter Zhang Jiaxing)
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