They create a new version of CAR-T therapy that can be used in solid tumors

CAR-T cell therapy is increasingly used against blood cancers and a team has now tested, with mice, an adaptation to also treat tumors solids, an advance that could transform the treatment of that disease.

Researchers at the Albert Einstein College of Medicine in New York lead a study published in Science Advances that describes this new version.

CAR-T cell therapy, which boosts the immune system to identify and attack cancer cells, has revolutionized the treatment of blood cancers such as leukemia and lymphoma.

However, it has not worked well against solid tumors, so the team, led by Xingxing Zang, introduced changes to this standard therapy to enhance its effectiveness against cancers such as pancreas and glioblastomas.

Five adaptations

Specifically, they created five adaptations that they tested in mice implanted with various types of solid human tumors. One of them, called TOP CAR, was shown to be superior in safely and effectively reducing not only glioblastoma and pancreatic tumors, but also lung cancer tumors.

CAR-T cell therapy, short for chimeric antigen receptor (CAR)-T cell therapy, transforms T cells (a type of immune cell) into cancer seekers programmed to attack on contact.

The patient’s T cells are extracted and genetically modified to express synthetic CAR receptors, which can recognize specific proteins, known as antigens, that protrude from cancer cells.

The engineered T cells reinfused into the patient can, thanks to their new CARs, locate cancer cells and attack them.

CARs contain four key proteins and in the new study the team achieved success against solid tumors by altering two of them, the Albert Einstein College of Medicine explained in a statement.

The five adaptations developed by the team used the same novel target protein, a monoclonal antibody that binds to B7-H3, a cancer cell antigen widely expressed in most solid tumors and their blood vessels.

The goal is for CARs to not only attach T cells to solid tumors, but also, by specifically binding to B7-H3, prevent it from interfering with the T cells’ ability to attack and destroy cancer cells and their blood vessels.

Additionally, CARs also had to include a costimulatory protein that helps activate T cells once they come into contact with cancer cells.

TOP CAR therapy uses as a costimulator a protein that had not been tested in CAR-T, it is TMIGD2, which could give CAR-T cells “the activation impulse they need to reach cancer cells and persist within solid tumors”Zang explained.

Seven out of nine mice survived

CAR-T therapy with TOP CAR (TMIGD2 potency/persistence optimized CAR) was shown to be the best in keeping mice with pancreatic, lung and glioblastoma tumors alive.

The treatment allowed seven out of nine mice with glioblastoma tumors to survive, compared with a maximum survival of three out of nine mice achieved by any of the other CAR-T therapies, and was superior in terms of key efficacy and safety parameters.

Zang wants to continue developing TOP CAR until it becomes a platform “ready to use” that can be simultaneously directed against B7-H3 and other tumor antigens, which can be easily adapted to the treatment of many different types of solid tumors.

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