- Jan 27, 2018
Cancer cases that emerged in a sister drug's clinical trial definitely set back Bluebird Bio and its one-time blood disorder gene therapy Zynteglo. But the incident could ripple beyond Bluebird's specific products as the EMA vows to look into "similar medicines under evaluation."
A salient point from the article:
“The question focuses on whether Zynteglo’s lentivirus vector inserted itself into the human genome to cause cancer. Even though no other approved medicines use the same viral vector—as the EMA noted—analysts at Jefferies and J.P. Morgan figure the problem could reach beyond Bluebird.”
Salient points from this article:
“FROM FAILED GENE THERAPY TO VACCINE
Adenovirus vaccines might be grabbing the limelight amid the coronavirus pandemic, but they have a checkered past.
When scientists began creating adenoviral vectors in the 1980s, most worked with a particular kind of adenovirus called Ad5, which ubiquitously infects humans and causes the common cold. Researchers stripped Ad5 of the genes it needed to replicate and inserted those genes into genetically engineered cell lines. That ensured that the modified viruses could be grown only in these special cells in the lab. It also opened up space in the Ad5 genome for scientists to stitch in new genes of their choosing.
Many scientists hoped to use Ad5 to deliver a human gene that could correct rare genetic mutations—an approach called gene therapy.
Those efforts came to a grinding halt in 1999 when a teenage boy with a rare genetic liver disease died after receiving an injection of an Ad5-based gene therapy, which had been designed in James Wilson’s lab at the University of Pennsylvania.
The large dose of 38 trillion viruses the patient was given sparked massive body-wide inflammation and sent his immune system into overdrive. After that, scientists mostly stopped using adenoviral vectors for gene therapy, in which the dose needs to be high to reach many cells of the body.
But vaccine developers viewed adenovirus-induced inflammation as an asset.
“There is an expression out there that a failed gene therapy makes a good vaccine,” says Luk Vandenberghe, a viral vector expert at Harvard Medical School.“
“Compared with some of the newer, experimental technologies—such as Moderna’s mRNA vaccine, which was the first to enter human trials in the US—adenoviral vectors are touted as a more tried-and-true approach. J&J calls its adenoviral vector platform a “proven” technology. While adenoviral vectors have been tested in far more people than mRNA vaccines, the technology is used in only one commercial vaccine today: a rabies vaccine used to immunize wild animals. So far, no adenoviral vector vaccines have demonstrated they can prevent disease in humans.
“It is not proven until it is licensed, and in postlicensure, continues to succeed,” Ertl says. “To say it is proven without peer-reviewed efficacy data is a stretch.”
Here’s what I’m wondering...if Bluebird’s gene therapy MAY have inserted itself so as to trigger cancer causing genes...who’s to say adenovirus vector vaccines (which are based on failed gene therapy programs) could not also have that potential?