March 2022: A revolutionary approach to CAR-T Cell therapy has the potential to overturn what has become a medical axiom: that the treatment’s remarkable effect on tumours comes at the expense of substantial hazards to patient safety.
Patients treated with a slightly modified version of an approved CAR-T experienced advantages comparable to earlier studies, but without the typical adverse effects that sometimes send patients to the hospital and necessitate costly additional treatments.
According to data released recently, the trial only enrolled 25 individuals in China. Experts believe that if the findings can be duplicated, a little molecular tinkering could make CAR-T safer and more readily available.
“This appears to be very promising,” said Jill O’Donnell-Tormey, CEO of the Cancer Research Institute, a non-profit organisation. “Obviously, it’s early in the game, but the response they’ve gotten from the 25 people they’ve seen thus far is astounding.”
CAR-T treatments are made by taking a patient’s own immune cells, genetically modifying them to target tumours, and then injecting them with substances that encourage the body’s natural defences to join the fight. Scientists focused on the final phase in the procedure to create a safer medicine.
They started with Novartis’ Kymriah, which was approved to treat two types of blood malignancies, and then created their own analogues, each sewn together with a slightly different amino acid sequence. They noticed something interesting when they tried these mutations in mice: One of the modified CAR-Ts was able to kill cancer cells without inducing a feverish immune response or generating brain inflammation, which are two of the most prevalent significant side effects of cell treatment.
It also passed human testing. The altered Kymriah caused no major cases of cytokine release syndrome, an immune flareup frequent in CAR-T cells, and no neurotoxicity, according to the study published in Nature Medicine. In Novartis’ published research, however, more than half of the patients had cytokine release, and around a quarter had neurological issues.
Dr. Si-Yi Chen, an immunology professor at the University of Southern California and the paper’s primary author, stated, “That was a really huge surprise to us.” Chen’s coworkers were also taken aback.
The modified CAR-T looked to have found an immunological sweet spot, attracting just enough cytokines to have an effect on cancer without causing any havoc. However, it is unclear why this is the case. It’s possible that licenced CAR-Ts like Kymriah and Gilead Sciences’ Yescarta are just too powerful, and that a lesser therapy can achieve the same results with less risk. It could also be a matter of chance.
Dr. Loretta Nastoupil, chief of the lymphoma department at MD Anderson Cancer Center in Houston, said, “I would look at this with a bit of caution, or cautious hope.” “Understanding the processes behind its efficacy will be crucial.”
There’s also the issue of long-term viability, which goes beyond the fundamental science. Approved CAR-Ts frequently result in long-term remissions. Dr. Michel Sadelain, an immunologist at Memorial Sloan Kettering Cancer Center, said Chen’s strategy appears to be safer in the short term, but it has to be seen whether the effects will last.
“The problem is that if you weaken the CAR, that’s terrific if you reduce cytokine production, but may you reduce the therapeutic effect?” Sadelain explained. “Here’s where the huge question mark is. “Only time will tell,” says the narrator.
Aside from those concerns, the prospect of a safer CAR-T could significantly expand access to a treatment that is currently only available at large cancer institutions. The treatment’s side effects frequently necessitate specialist care and expertise not accessible at community hospitals, which limits the number of patients who can be treated.
Then there’s the price. The cost of a CAR-T treatment is upwards of $370,000 per treatment, although that does not include the cost of hospitalisation or immune-suppressing medicines. According to Avery Posey, an immunotherapy researcher at the University of Pennsylvania, the final cost in the most severe cases frequently approaches $1 million.
“What the residents at Penn call ‘CAR-Tastrophy,'” Posey said of the mix of immunological adverse effects and neurotoxicity.