April 18, 2024

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Hemophilia Patients suffer from liver cancer after gene therapy vector

Hemophilia Patients suffer from liver cancer after gene therapy vector

Hemophilia Patients suffer from liver cancer after gene therapy vector.  Science: The most “safe” gene therapy vector does not seem to be safe. Patients with hemophilia suffer from liver cancer after treatment. 

For a long time, adeno-associated virus vector (AAV) has been recognized as the most ideal gene therapy gene vector at present because of its long-term latency in the human body without showing any obvious pathogenicity. However, in recent years, there have been constant voices reminding that this seemingly safe treatment may be fatal.

On December 22, local time, “Science” published an article titled “Liver tumor in gene therapy recipient raises concerns about virus widely used in treatment”, which once again confirmed this view. According to the report, a gene therapy for hemophilia B by the Dutch biopharmaceutical company uniQure was stopped by the US FDA because the patient developed hepatocellular carcinoma after treatment.

Hemophilia Patients suffer from liver cancer after gene therapy vector 

doi: 10.1126/science.abg2917

At the center of public opinion is a gene therapy based on the AAV5 viral vector, which has previously been awarded the designation of breakthrough therapy by the FDA and the designation of PRIME by EMA. Judging from the previous clinical data, this therapy is quite effective.

In 2019, uniQure shared the Phase 2 clinical data of the therapy at the 27th International Society for Thrombosis and Hemostasis (ISTH), showing that the FIX activity of three patients reached 54% of the normal value after 36 weeks of treatment, and the average value was normal 45% of the value.

The phase 3 clinical trial that was shelved this time involved 54 patients. At the 62nd Annual Meeting of the American Society of Hematology just past, uniQure shared the initial experimental data, which showed that after 26 weeks of administration, the patient’s FIX level increased from ≤2% to 37.2%, reaching the primary endpoint of the trial and receiving one time Six months after sex gene therapy, the critically ill patient seems to have transformed into a functionally cured state.

According to the statement issued by uniQure this time, there is reason to believe that the underlying disease in the patient’s body may cause him to develop cancer. According to reports, this liver cancer patient was infected with hepatitis B virus and hepatitis C virus 25 years ago, and chronic infection of these viruses is related to 80% of hepatocellular carcinoma. Nevertheless, the more important issue is to determine whether AAV gene therapy is related to this event, or promoted the occurrence of liver cancer in patients.

In November 2020, “Nature Biotechnology” published a research paper titled A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. The article mentioned that after 10 years of AAV gene therapy on 9 dogs with hemophilia A, it was discovered that some of the therapeutic gene fragments carried by the AAV virus were integrated into the dog’s chromosomes near the genes that control growth, indicating that they could induce cancer. possibility.

Hemophilia Patients suffer from liver cancer after gene therapy vector


Prior to this, gene therapy for AAV blood diseases has been shown to be at risk of liver damage. In 2001, a clinical trial of AAV2 (containing the FIX gene) conducted by the Children’s Hospital of Philadelphia reported liver damage, as did clinical trials of other types of AAV vectors.

David Lillicrap, a hemophilia researcher at Queen’s University in Canada, said: “Although this liver cancer patient has been treated for a short period of time, it seems unreasonable to attribute the cancer to AAV gene therapy, but if the patient has already developed a slow growth Liver masses, AAV may be inserted into the DNA of his liver cells in a way that can stimulate cancer cells to grow faster.”

This may also be a shortcoming of uniQure’s study, and it did not exclude people with previous HCV and HIV infections. The company is currently cooperating with the FDA to investigate the cause behind this incident, and it is expected that the results of the investigation will be obtained in early 2021.


(source:internet, reference only)

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