After infecting the new coronavirus, the tumor actually cured?! This case is

PD-1 inhibitors (hereinafter referred to as PD-1) are not omnipotent, but also resistant

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For patients with advanced cancer who regard PD-1 as the last straw, drug resistance undoubtedly means that the light of survival is dying

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Therefore, how to solve the problem of PD-1 resistance is an urgent problem to be solved

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Recently, the international journal “thoracic cancer” published “the world’s first case of non-small cell lung cancer (NSCLC) patients receiving recombinant human type 5 adenovirus therapy to reverse PD-1 drug resistance”, which brought new dawn for clinical solution to this problem and aroused international attention

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Ding Xiangyuan has the honor to invite Professor Miao Liyun, the doctor in charge of this patient and the main author of this article, to reveal the true situation of this case and the latest research progress of using oncolytic virus therapy to reverse PD-1 resistance in the world

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Death sentence! For lung cancer patients who have been treated for six years, drug resistance will inevitably appear in the final plan PD-1

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“Let’s take a look at such a lung cancer patient who was” sentenced to death “in a 3A hospital.” Professor Miao first talked about the basic situation of this patient

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In January 2015, a 57 year old female patient was diagnosed as right lung mucinous adenocarcinoma for the first time

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In 2015, she underwent radical resection of right lower lung cancer without postoperative adjuvant chemotherapy; In 2017, the right lung mucinous adenocarcinoma recurred, and received platinum containing two drug chemotherapy regimen plus anti angiogenesis drugs

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Due to the progress of the disease, the chemotherapy drugs were changed many times; In February 2019, the patient was treated with PD-1 single drug “navulizumab”

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Two months later, the disease progressed; They were treated with PD-1 combined with chemotherapy and bevacizumab; In June 2020, the disease progressed again and the symptoms worsened

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The performance status (PS) score was 3-4

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Professor Miao said in an interview, “based on past experience, this patient has developed PD-1 resistance, and there is no drug available under current medical conditions.” Amazing reversal! PD-1 immunotherapy combined with oncolytic virus can stabilize the patient’s disease

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Professor Miao and his team are not reconciled

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On the one hand, the patient has a very strong desire for survival

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On the other hand, the patient’s wonderful life in the latter half of his life is about to start, and he wants to bring hope for the patient’s next life

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Oncolytic virus therapy is a kind of treatment method that directly acts on tumor cells

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Its principle is to genetically modify the naturally existing virus with weak pathogenicity to form oncolytic virus, which selectively replicates in tumor cells by using aberrant signal pathways (such as inactivation or defect of tumor suppressor gene) in cancer cells, leading to tumor cell lysis and death

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At present, the clinical application of oncolytic virus has experienced many ups and downs, and is in the upsurge of research and development

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In the following days and nights, Professor Miao’s team searched a large number of literatures and found that previous basic studies abroad showed that “oncolytic virus can reverse PD-1 drug resistance”, but these animal studies mainly focused on melanoma and other tumors

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At the same time, Professor Miao mentioned that recombinant human adenovirus type 5 injection has been on the market for more than ten years in China

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In view of the poor operability, high risk and side effects of intra tumor injection in lung cancer, there are no more reports on the application of recombinant human adenovirus type 5 injection in the treatment of lung cancer This patient has no other treatment options, we decided to implement oncolytic virus combined with immunotherapy

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Soon, we had full communication with the patient and his family, and the patient was very willing to try

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So we got in touch with the company that produced recombinant human adenovirus 5 injection and obtained several drugs

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” Professor Miao gave Ding Xiangyuan a detailed description of the treatment process

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Professor Miao’s team injected recombinant human adenovirus type 5 at a suitable location inside the tumor, and continued to give PD-1 treatment

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More than 20 days later, the family members excitedly called to say that the patient’s symptoms were obviously improved (cough relieved, wheezing improved), and they were willing to continue the program

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Considering the overall drug tolerance, only PD-1 was given

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When the tolerance was further improved, the patient was injected with recombinant human adenovirus type 5 for the second time, and the symptoms were improved again

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He was able to get out of bed and exercise, and his endurance was getting better and better

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As a result, two more injections were followed, with a total of four injections

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At the fourth time, the patient’s symptoms were significantly improved, and the imaging also showed that the tumor was obviously absorbed and improved (Fig

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1) As of January 7, 2021 before the publication of the article, patients not only showed stable disease in the evaluation of tumor efficacy, but also improved PS score from the initial 4 points to 1 point, “Professor Miao told Ding Xiangyuan

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A ~ g are the chest CT images of patients at different time points, in which a ~ d are from July 2017 and February, April and November 2019 respectively; E is in June 2020, indicating the further development of the disease; The three pictures of F show that recombinant human adenovirus type 5 was injected into three lesions of the patient respectively; G was published in December 2020, which showed that although some lung tissues were necrotic, the disease was stable

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Figure 1 chest CT scan imaging of patients yes, it created a miracle! From the patient’s point of view, the curative effect of oncolytic virus combined with immunotherapy has been fully reflected

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So the safety in the process of medication is what we are particularly concerned about

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In this regard, Professor Miao Liyun said, because it is intratumoral injection of virus, the main purpose is to make the virus expand in tumor cells, just like a cold or viral pneumonia, the main side effect is fever

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But this kind of fever is in the acceptable range, the duration will not be too long, generally 3-4 days, with antipyretic analgesics can be solved

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Special attention should be paid to the “problems of intratumoral injection methods”

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This is equivalent to the respiratory department or interventional department to do percutaneous lung biopsy, some patients are prone to complications in the injection process, such as pneumothorax, bleeding

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Hemoptysis is a common complication, we must do a good job in prevention and treatment, otherwise massive hemoptysis may endanger life

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In conclusion, the main side effects in the treatment of recombinant human adenovirus type 5 are caused by puncture, while the drug itself does not have too many side effects

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Active exploration! Oncolytic virus combined with PD-1 immunotherapy has become a global research hotspot

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There are two drug resistance problems caused by PD-1 immunotherapy: “primary drug resistance” and “secondary drug resistance”

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Professor Miao said that the above case solved the problem of “secondary drug resistance” of the latter

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On the basis of previous studies, the case confirmed that “oncolytic virus can not only control the tumor focus, but also significantly improve the survival status of patients.”

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At the same time, to solve the problem of “primary drug resistance” of the former, oncolytic virus combined with PD-1 has been used as the first-line clinical treatment for patients with initial immune resistance, especially in melanoma and head and neck tumors We can see on the global clinical trials website (ClinicalTrials

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Gov) that there are four or five clinical studies on PD-1 or PD-L1 combined with oncolytic virus therapy in 2020 alone

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Therefore, it is not difficult to see that the joint use of oncolytic virus and PD-1 / PD-L1 is currently under active exploration in the world

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” Finally, Professor Miao explained the principle behind the incredible medical “miracle” that “infection with new coronavirus can cure tumor” which was constantly seen in the newspapers, and whether the tumor regression is related to the role of oncolytic virus

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Professor Miao Liyun said that reports of tumor disappearance caused by infection with bacteria, fungi or viruses were common in newspapers

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Popular to explain, that is, after infection with pathogens, the body’s immunity will be rapidly enhanced, resulting in anti-tumor effect.

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