A new generation of CAR T-cell immunotherapy shows promising results in preclinical models of malignant mesothelioma, prompting researchers to suggest the treatment should be evaluated in clinical trials.
In contrast to earlier versions of CAR T-cell treatments, it is considered more difficult for a tumor to grow resistant to the new treatment — called T4 immunotherapy by scientists — since the new generation of engineered immune cells targets a host of cancer-specific molecules.
The study, “Intracavitary ‘T4 immunotherapy’ of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells,” was published in the journal Cancer Letters.
Several studies propose that immunotherapy may be a good approach to treating mesothelioma, and clinical trials of immune checkpoint blockers are ongoing.
CAR T-cell therapy — a different kind of treatment, involving the re-engineering of a patient’s immune T-cells — has not proved to be effective against solid tumors. This is in part because of the difficulties in getting enough cells to the tumor site. But researchers at King’s College London in England argued that mesothelioma may be a special case, since the cells can be delivered straight into the affected body cavity.
To test this theory, the research team developed a new type of CAR T-cells designed to recognize molecules belonging to the ErbB family. These factors, also known as EGFR and HER2, among others, are present in the majority of mesothelioma tumors. The cells respond to the immune mediator IL-4, which makes them multiply in a lab dish.
To test whether the cells, created from patient-derived immune cells, were effective in combating mesothelioma, the researchers first performed a set of experiments in lab-grown cells. Using four different mesothelioma cell lines, they showed that the CAR T-cells became activated, releasing large amounts of cytokines, when they encountered the tumor. All four mesothelioma cultures were destroyed by the CAR T-cells.
The team then continued to examine the effects in mice which had human mesothelioma cells injected into the peritoneal body cavity. The treatment was able to shrink the tumors in all mice, and completely eradicated it in two of the five mice.
Importantly, researchers did not note any toxic effects of the treatment, suggesting that it may be a good candidate to explore in human clinical mesothelioma trials.