New CAR-T Cell Therapy for Mesothelioma Circumvents Immune Suppression

A new cancer treatment based on CAR-T cell therapy may have found a way to undermine a key protective mechanism in mesothelioma tumors.

The treatment is called UCARTMESO. It is being developed by a French biopharmaceutical company called Cellectis.

UCARTMESO targets cells that overexpress the protein mesothelin. It undermines some key genes in these cells preventing them from sending immune suppressive signals. 

Immune suppressive elements in the area surrounding mesothelioma tumors have historically kept CAR-T cell therapy from working as well as it does for some other types of cancer. 

But the developers of UCARTMESO say their approach may finally make CAR-T cell therapy a viable option for patients fighting asbestos cancer.  They presented their findings at the Society for Immunotherapy of Cancer conference in November. 

Immunotherapy with CAR-T Cell Therapy 

CAR-T cell therapy is a type of immunotherapy. Immunotherapy harnesses the power of the patient’s own immune system to fight their cancer. 

The therapy involves taking some of the patient’s immune system T-cells and altering them in the lab. When they are put back into the body, the altered T-cells seek out mesothelioma cells because they overexpress mesothelin. Normal cells express very little mesothelin, so the CAR-T cell therapy is less likely to affect them. 

When they encounter mesothelioma cells, the altered T-cells change the way the cancer cells function. Normally, mesothelioma tumors emit signals that alter the environment around them. This is one of the ways they keep the immune system from attacking them. 

But UCARTMESO CAR-T cell therapy interferes with the process that helps create this protective barrier. The area around the tumor – the tumor microenvironment – is no longer a safe space for mesothelioma to grow unchecked. Cancer killing immune system cells are then free to do their jobs. 

A New Way to Treat Mesothelioma?

There are a handful of treatments that may help keep mesothelioma tumors from growing. The typical first-line treatment is chemotherapy. Patients who are healthy enough may go on to have surgery. Radiotherapy is sometimes used to shrink tumors prior to surgery or to keep them from coming back, but it is not a primary mesothelioma treatment. 

Immunotherapy is a relatively new approach to mesothelioma. The FDA has approved a combination of Yervoy and Opdivo as an alternative to chemotherapy for mesothelioma. 

The FDA has not yet approved CAR-T cell therapy for mesothelioma. But early results look promising for UCARTMESO. Cellectis researchers say it “demonstrated potent activity” against mesothelioma cells in the lab and in live mice. 

In a statement, Laurent Poirot, PhD, Senior Vice President of Immunology at Cellectis said, “Overall, the data demonstrated that the TGFBR2 gene knock out provides valuable additional properties to UCARTMESO, which may result in a very effective therapy despite an immune suppressive tumor microenvironment, and supports its clinical development for the treatment of solid tumors.”

Sources:

Schiffer-Mannioui, C, et al, “UCARTMESO: Mesothelin (MSLN) targeting allogeneic CAR-T cells engineered to overcome tumor immunosuppressive microenvironment”, PowerPoint Presentation, Society for Immunotherapy of Cancer conference, November 2021, file:///home/chronos/u-bdbd0e70dd4e296c44f560f2a9c0d3504abc4109/MyFiles/Downloads/UCARTMESO_SITC_Poster_143__FINAL.pdf

Cellectis Presents First Preclinical Data on UCARTMESO, an Allogeneic CAR-T Cell Product Candidate Targeting Mesothelin to Treat Solid Tumors at the Annual Meeting of the Society for Immunotherapy of Cancer, New Release, November 11, 2021, Cellectis website, https://www.cellectis.com/en/press/cellectis-presents-first-preclinical-data-on-ucartmeso-an-allogeneic-car-t-cell-product-candidate-targeting-mesothelin-to-treat-solid-tumors-at-the-annual-meeting-of-the-society-for-immunotherapy-of-cancer/