August 17, 2022

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Cancer patients is hopeless if PD-1 resistance occured?

Cancer patients is hopeless if PD-1 resistance occured?

 

Cancer patients is hopeless if PD-1 resistance occured?  Many PD-1 monoclonal antibodies have been approved. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused by it will also receive more and more attention.

Immunotherapy represented by PD-1 inhibitors (hereinafter referred to as PD-1) is an important treatment for cancer patients, but patients after drug resistance are still facing the desperate situation of “no medicines available”.

The basic research on the reversal of PD-1 resistance by oncolytic viruses has long attracted the attention of the industry. In February of this year,  A meidcal team published in the international journal Thorac Cancer, “The world’s first non-small cell lung cancer (NSCLC) patient received oncolytic virus treatment to reverse PD-1 resistance”, from The clinical practice has verified the efficacy of oncolytic viruses. 

 

For patients who have been treated for lung cancer for 6 years, resistance to PD-1 will inevitably appear in the ultimate plan

Let’s see a case as below: 

  • In January 2015, a 57-year-old female patient was diagnosed with right lung mucinous adenocarcinoma for the first time and underwent radical resection of right lower lung cancer in 2015, without postoperative adjuvant chemotherapy;
  • In 2017, the right lung mucinous adenocarcinoma recurred and was given a platinum-containing two-drug chemotherapy regimen + anti-angiogenic drugs, and the chemotherapy drugs were changed many times due to disease progression;
  • In February 2019, he was treated with PD-1 single-drug “nivolumab”, and the disease progressed 2 months later;
  • Treated with PD-1 combined with chemotherapy and anti-angiogenic drug bevacizumab, and changed the combined drug several times due to disease progression;
  • In June 2020, the disease progressed again and the symptoms became worse, and the performance status (PS) score was 3 to 4 points.

Based on past experience, this patient has developed PD-1 resistance, and there is no medicine available under current medical conditions.

 

PD-1 immunotherapy combined with oncolytic virus, the patient got stable disease

The medical team are not reconciled. On the one hand, the patient has a very strong desire to survive. On the other hand, the wonderful life of this patient is about to start in the second half of his life. He wants to bring hope to the patient.

Oncolytic virus therapy is a treatment method that directly acts on tumor cells. Its principle is to genetically modify naturally-occurring viruses with weaker pathogenicity to form oncolytic viruses, using aberrant signaling pathways in cancer cells (such as tumor suppressor). Gene inactivation or defect) selectively replicates in tumor cells, leading to tumor cell lysis and death. At present, the clinical application of oncolytic viruses has experienced many ups and downs, and is currently in the process of research and development.

In the following days and nights, the medical team searched a large number of documents and found that there were basic studies abroad that showed that “oncolytic viruses can reverse PD-1 resistance”, but these animal studies are mainly for melanoma and other tumors. At the same time, the doctor mentioned that some countries’s recombinant human adenovirus type 5 injection has been on the market for more than ten years. In view of the poor operability of injection into lung tumors, the greater risks and side effects, there is no more application in the treatment of lung tumors Report.

“This patient has no other treatment options. We decided to implement an oncolytic virus combined immunotherapy program. Soon, we communicated fully with the patient and his family, and the patient expressed his willingness to try. So we cooperated with the production of recombinant human 5 The company of type adenovirus injection got in touch and obtained several medicines.” the doctor gave a brief account of the treatment process that he had just experienced to Dingxiangyuan reporter.

The medical team injected recombinant human type 5 adenovirus into a suitable place inside the patient’s tumor and continued to give PD-1 treatment. More than 20 days later, the family members called excitedly and said that the patient’s symptoms had improved significantly (cough lessened, wheezing improved) and they were willing to continue the treatment.

Taking into account the overall tolerance of the drug, only PD-1 treatment was given afterwards. When the tolerance improved further, after the second injection of recombinant human adenovirus type 5, the patient’s symptoms improved again, she was able to get out of bed, and her endurance got better and better. Therefore, two more injections were made afterwards, for a total of four injections before and after. In the fourth time, not only the symptoms of the patient were significantly improved, but the imaging studies also showed that the tumor was absorbed and improved significantly (Figure 1) [1].

“As of January 7, 2021 before the article was published, the patient not only showed stable disease in the tumor efficacy evaluation, but also the PS score improved from the initial 4 points to 1 point,” the doctor told reporters, with a hint in his words. Excited.

a ~ g are the chest CT images of the patient at different time points, where a ~ d are from July 2017 and February, April, and November 2019 respectively; e is from June 2020, showing the further development of the disease; f The 3 pictures in are the injection of recombinant human adenovirus type 5 into the patient’s three lesions; g is from December 2020, showing that although part of the lung tissue is necrotic, the disease has been stabilized.

Cancer patients is hopeless if PD-1 resistance occured?

Figure 1 CT scan imaging of the patient’s chest

Yes, this has created a miracle! From the perspective of patients, the efficacy of oncolytic virus combined immunotherapy has been fully demonstrated.

Then, the safety of the medication is also of special concern to us.

In this regard, Hopeless for cancer patients if PD-1 resistance occured.  Many PD-1 monoclonal antibodies have been approved. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused by it will also receive more and more attention. said that because the virus is injected into the tumor, it is mainly to allow the virus to expand in the tumor cells. Just like a cold or viral pneumonia, the main side effect is fever. But this kind of fever is within the acceptable range, and the duration is not too long, usually 3 to 4 days, it can be resolved with antipyretic analgesics. What needs special attention is the “problems of intratumoral injection.”

This is equivalent to doing a percutaneous lung biopsy in the respiratory department or interventional department. Some patients are prone to complications during the injection process, such as pneumothorax and bleeding. Hemoptysis is a common complication, and preventive measures must be taken. Otherwise, massive hemoptysis may be life-threatening.

In short, the treatment of recombinant human adenovirus type 5 is mainly the side effect caused by puncture, and the drug itself does not have many side effects.

 

Oncolytic virus combined with PD-1 immunotherapy has become a global research and development hotspot

There are two drug resistance problems caused by PD-1 immunotherapy: “primary drug resistance” and “secondary drug resistance”.  The doctor said that the above case solves the problem of the latter’s “secondary drug resistance”.

Based on previous studies, this case confirmed that “oncolytic viruses can not only control tumor lesions, but also make the patient’s survival status meaningful. improve”.

At the same time, in response to the former problem of “primary drug resistance”, the first-line clinical treatment of oncolytic virus combined with PD-1 is currently available internationally for patients with initial immune resistance, especially in melanoma and head and neck tumors. high.

“We can see on the global clinical trial website (ClinicalTrials.gov) that in 2020 alone, there will be four or five clinical studies on PD-1 or PD-L1 combined with oncolytic virus treatments underway. Therefore, it is not difficult to see The combined use of oncolytic viruses and PD-1/PD-L1 is currently being actively explored globally.”

Finally, for the incredible medical “miracle” that “infection with the COVID-19 virus can treat tumors” that has been constantly seen in the newspapers, Hopeless for cancer patients if PD-1 resistance occured.  Many PD-1 monoclonal antibodies have been approved. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused by it will also receive more and more attention. explained the principle behind it and whether this tumor regression is related to the effect of oncolytic viruses.

Hopeless for cancer patients if PD-1 resistance occured.  Many PD-1 monoclonal antibodies have been approved. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused by it will also receive more and more attention. said that reports of tumor disappearance caused by infection with bacteria, fungi or viruses are common in the newspapers. In layman’s terms, after infection with pathogens, the body’s immunity will be rapidly strengthened, resulting in an anti-tumor effect. Tumors can survive in the body because they steal the body’s immune tolerance secrets, so that immune cells cannot recognize it. The injected virus, fungus, etc. replicate in tumor cells to make tumor antigen expression specific, so that the body’s immune system can recognize tumor cells and kill them.

“The reported cases of disappearance of COVID-19 pneumonia tumors are both in hematological tumors and lung cancer. It is the infection that opens the door for the body to attack the tumor. It can also be said that this is the effect of an oncolytic virus.”

Regarding this “miracle” of cancer treatment, Hopeless for cancer patients if PD-1 resistance occured.  Many PD-1 monoclonal antibodies have been approved. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused by it will also receive more and more attention. emphasized that he firmly does not advocate that cancer patients take the initiative to infect the virus, because there are many uncontrollable factors after infection.

 

Summary

Nowadays, a number of PD-1 monoclonal antibodies have been approved in China. It is foreseeable that the clinical use of PD-1 will be expanded on a large scale, and the drug resistance problem caused will also receive more and more attention.

The oncolytic virus mentioned in this article reverses PD-1 resistance cases, which is a successful exploration of such patients and provides us with a good idea to solve the problem of resistance. Of course, the program still needs further research and verification.  Sicentists and Doctors will continue to explore this topic in the future to help patients overcome difficulties, overcome tumors, and improve their survival status.

 

(source:internet, reference only)


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