Hot Topic: Will in vivo breathe new life into CGT?
It’s now almost nine years since the first CAR-T therapies, Kymriah and Yescarta, were approved by the FDA.
These therapies and others have revolutionised the treatment of certain hard-to-treat blood cancers, such as ALL and some B-cell lymphomas.
There was rightly huge elation at the time.
CAR-Ts were a real breakthrough, offering a lifeline – particularly to younger patients, who’d previously had little chance of beating their cancer.
But the past decade has been a frustrating one for developers of CAR-Ts, and other cell therapies.
The scientific and medical breakthrough, has not been matched by commercial success.
The treatment process is simply too slow and too expensive.
First you have to extract a patient’s blood,
- Then separate and collect their T-cells,
- Then genetically engineering them with Chimeric Antigen Receptors in the lab
- Then multiply the cells,
- And then infusing them into the patient.
It’s like trying to make a Saville Row suit for everyone.
The consequent price tag, which can exceed half a million dollars, has been off-putting too.
As a result, the investment appetite for CAR-Ts has dimmed.
But the CAR-T field is now getting a shot in the arm, thanks to the first real signs of success in developing in vivo CAR-T technology.
In vivo CAR-T involves doing the genetic manipulation inside the body – injecting the instructions so the patient’s T-cells learn to recognise their target, rather than having to take the cells out and do it “by hand”.
At ASCO in Chicago, Kelonia – which was bought by Eli Lilly earlier this year for up to $7bn – presented knock-out data for its in vivo CAR-T, KLN-10-10, in relapsed / refractory multiple myeloma patients.
These are heavily pretreated patients who’d stopped responding to prior treatments.
This has been considered an untreatable form of the disease, a death sentence.
But Kelonia got a 100% response rate in 18 patients it treated with KLN-10-10 – with every single one of them being cancer-free a month after treatment.
The first four to be treated remain apparently disease-free up to 10 months after treatment. They are still being monitored.
A Lilly executive described the results as “nutty”.
This is the biggest and furthest down the line in vivo CAR-T success so far, but it isn’t the only one.
Together, they are prompting a re-evaluation – not just of CAR-T, but of cell therapies more generally, and potentially gene therapies too.
Because if in vivo can move away the CGT model away from ‘tailor made’ and towards ‘production line’, that really will be a game-changer.
