The cure to cancer may not be hidden in some drug or chemical but within our own body. A team of Chinese researchers recently conducted a clinical trial that showed that genetically modified immune cells can increase the chances of survival for patients with gastric and gastro-oesophageal junction cancer, a deadly type of stomach cancer.
This therapy is called satricabtagene autoleucel (satri-cel), and it uses CAR (Chimeric Antigen Receptor)-T cells (modified immune cells) to kill cancer cells. Previously, this therapy was mostly used to treat blood cancers. However, the new test marked the first global randomized controlled trial of CAR-T cell therapy in patients with hard-to-treat solid tumors.
“Solid tumours generally don’t respond well to CAR-T-cell therapy. The trials are among the first in which CAR-T-cell therapy has had promising results against solid tumours,” Lisa Mielke, a cancer researcher from Australia, said. She wasn’t involved in the study.
Treating stomach cancer like never before
Treating solid tumours with CAR-T cell therapy has been a long-standing challenge in oncology. Unlike blood cancers, solid tumours form dense tissue barriers and often lack a unique target protein that immune cells can attack without harming healthy cells.
That’s where this study can make a difference. It focused on a protein called CLDN18.2, which is found in high amounts on certain stomach cancer cells but rarely appears in normal tissues. This made it an ideal target for an immune attack.
A trial, named CT041-ST-01, was conducted in China and involved 156 patients with advanced gastric or gastro-oesophageal junction cancer. All participants had already undergone, and failed, at least two previous rounds of conventional treatment.
The group was divided in a 2:1 ratio: 104 patients received satri-cel, while 52 got the physician’s choice of standard treatment (including drugs like paclitaxel and nivolumab). The process began with doctors taking T cells from each patient and then reprogramming them in the lab to produce a special CAR receptor, designed to recognize and attach to CLDN18.2.
The modified cells were multiplied and then infused back into the same patient. These re-engineered cells are now capable of hunting down and killing the cancer cells carrying the CLDN18.2 protein.
Among those who received satri-cel, 88 patients got at least one dose, and each person received up to three infusions, with 250 million CAR-T cells per dose. The results were surprising. Patients in the satri-cel group had a median progression-free survival of 3.25 months, compared to 1.77 months in the control group.
This means their cancer stayed under control for nearly twice as long. There was also a 63% reduction in the risk of the cancer worsening or the patient dying. Importantly, 35% of satri-cel patients showed a clear tumour response, compared to just 4% in the control group. Overall, people who received satri-cel lived 2.4 months longer on average.
“Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile. These results support satri-cel as a new third-line treatment for advanced gastric or gastro-oesophageal junction cancer patients,” the study authors note.
Increasing the reach of CAR-T cell therapy
Until now, the biggest hurdle was finding a way for CAR-T cells to reliably reach and attack solid cancers without damaging healthy tissues. The success of satri-cel shows that, with the right target like CLDN18.2, these obstacles can be overcome. However, the therapy isn’t perfect and risk-free.
Nearly all patients (99%) experienced at least one moderate or severe side effect. For instance, a dangerous immune reaction called cytokine release syndrome (CRS), also known as cytokine storm, where the immune system goes into overdrive, occurred in 95% of patients, but these were mostly manageable with standard care, especially by doctors trained in using CAR-T therapies for blood cancers. The side effects of cytokine storm typically involve fever, muscle aches, and nausea.
The gains in survival were measured in months, not years, and that may seem insignificant to most people. However, for cancer patients with no other options, this could mean more meaningful time with family and a better quality of life.
Also, this was a phase II trial, and researchers are now planning further studies to test satri-cel in earlier stages of the disease, where patients may respond even better.
The details of the trial are published in the journal Lancet.
