CAR-T research is flourishing but is hampered by outdated precautions, experts say

Excerpt – “When we started in 2010, we were appropriately concerned that genetic engineering would create so-called Frankenstein cells that would be uncontrollable,” [professor at the University of Pennsylvania and a CAR-T pioneer Carl] June said. “There were lots of regulatory issues put in that has slowed research. But 11 to 12 years in, more than 20,000 people treated, and it’s never happened — the Frankenstein cell turned into a CAR-T tumor hasn’t happened. Autologous cells are safe, they don’t need to be regulated as in experimental, early stage by the FDA.” [..]

Innovation is needed in the CAR-T field, which has struggled with high costs and long wait times for the treatment. In some cases, patients who could benefit from CAR-T therapy and have no other options for treatment have died while on a waiting list to receive the cells. Other patients simply have not been able to get access to the treatment, said [co-founder of the More Moments More Memories Foundation Christi] Shaw, who is also a former biotech executive at Kite Pharma and Novartis and helped shepherd the development of some of the first CAR-T products.

“Only two out of 10 patients eligible to receive the therapy in lymphoma — this is a 50-50 chance of a cure in lymphoma — only two out of 10 patients get referred,” Shaw said. “Big pharma is distracted by problems they haven’t solved yet. If we can shift the focus of big pharma to innovation and actually fund more innovation, the more patients will be treated.”

Some of that innovation is happening in terms of manufacturing, Shaw said. Researchers are working on allogeneic or off-the-shelf CAR-T, created from healthy donors and theoretically able to sit frozen in storage until needed. Autologous CAR-T manufacturing is also accelerating. “If we can think about manufacturing not in a separate location but bringing it closer to treatment, then I think autologous can rival the real time you could get from future therapies in allo,” Shaw said. “Making it cheaper, at the site of the bed of the patient, and cost effective.”

Other groups are studying how to create CAR-T cells from stem cells, said Sadelain. “And a fourth approach, very daring but also tantalizing, is what if you can engineer cells in the patient’s body and actually circumvent this manufacturing,” he said. “That’s a long shot idea. To me, what’s very comforting and promising is that there’s all these possibilities.”

Full article, A Chen, STAT News, 2023.5.3