Media Thread, page-5104

A team at Penn says it has slashed CAR-T cell therapy manufacturing timeframe to just 24 hours
https://endpts.com/a-team-at-penn-says-it-has-slashed-car-t-cell-therapy-manufacturing-timeframe-to-just-24-hours/

Josh SullivanAssociate Editor

The future of CAR-T cell therapy research has come a long way over the years, but scientists have still been plagued by one problem: how to cut down on the timeframe, which typically takes between 9 and 14 days.

Except now. Researchers at Penn say that they have shortened the process, enhancing anti-tumor potency in just 24 hours. The preclinical study, carried out by researchers Michael Milone and Saba Ghassemi, has been published in Nature Biomedical Engineering. The results show the potential for a stark reduction of time, materials and labor that’s required to make CAR-T cells, which could be the most beneficial for those who are experiencing rapidly-progressing disease in environments with limited resources.

“In mouse xenograft models of human leukaemias, the rapidly generated non-activated CAR-T cells exhibited higher anti-leukaemic in vivo activity per cell than the corresponding activated CAR-T cells produced using the standard protocol,” the article says. “The rapid manufacturing of CAR-T cells may reduce production costs and broaden their applicability.”

The research builds upon work from 2018 that found a reduction in traditional manufacturing to just three days, Milone said in a statement. The group hopes that this will cut down the cost of the process, as well as the timeframe.“While traditional manufacturing approaches used to create CAR-T cells that take several days to weeks continue to work for patients with ‘liquid’ cancers such as leukemia, there is still a significant need to reduce the time and cost of producing these complex therapies,” he said.

The trick lies in the quality of the CAR-T cells, rather than the quantity, the team said. When removed from the body too long, T cells can lose the ability to replicate. That makes it less effective as a living drug, which is something the team at Penn set out to solve when starting its research. Research showed that smaller numbers of higher-quality cells generated without a lot of expansion outside the body perform better than a higher number of cells that were expanded outside the body before being returned to the patients.

Traditional manufacturing calls for T cells to be activated to replicate and expand in number. To work around this, Penn’s researchers originally used lentiviral vectors that come from the HIV virus to deliver the CAR gene to T cells. But the process wasn’t efficient, and so scientists worked to find a way to deliver the genes directly to non-activated T cells isolated from the blood. This sped up the process, and dually, did not allow patients to be infected with HIV during the process. The study can set up more research about how engineered CAR-T cells can work in patients with specific cancers. Some of the tech involved in the study has been licensed to Novartis, the release said.

“Not only might it improve the production capacity of centralized manufacturing facilities, but if simple and consistent enough, it might be possible to produce these therapies locally near the patient,” Ghassemi said in a statement. “Which could be tantamount to addressing the many logistical challenges that impede delivery of this effective therapy especially in resource-poor environments.”

Ghassemi does not have a background in biology, Milone said in a call Wednesday. But after a collaboration with Columbia, where she got her pHd in mechanical engineering, Ghassemi was so intrigued by the science of CAR T that she reached out to Milone and joined the his lab. While she was learning about vectors, Ghassemi asked Milone a simple question.“This project actually originated from a naive question: Why do we have to stimulate the T cells?” he said. “Well, we don’t. But the efficiency is low. So we started talking about that and asking how can we make this more efficient.”

Milone was a key part of the leadership team that developed Novartis’ breakthrough CAR-T drug Kymriah at Penn. In 2018, Milone cofounded a biotech dubbed Cabaletta Bio with Penn’s Aimee Payne and Steven Nichtberger to work with chimeric auto-antibody receptors. Earlier this month, Cabaletta was granted Fast Track Designation for MuSK-CAART, a treatment for the improvement of daily living and muscle strength in patients with MuSK antibody-positive myasthenia gravis.