Targeting Chondroitin Sulphate Proteoglycan 4 (CSPG4) in Glioblastoma
Remarkable elimination of leukemia has been achieved with a novel therapy in which specific cells collected from the blood, known as T lymphocytes, can be cultured and modified in the laboratory to express an artificial protein known as chimeric antigen receptor (CAR). When these cells are returned to the body, they can find the leukemic cells and kill them specifically. This clinical success encourages the development of a similar strategy for the brain tumor glioblastoma (GBM), which at the moment cannot be eliminated by surgery, chemotherapy or radiotherapy in either children or young adolescents.
We have constructed CAR and found that they can kill the majority of GBM tumor cells, but some of the tumor cells are capable of blocking the T lymphocytes that carry this CAR. We have identified how the tumor cells are blocking the T lymphocytes carrying the CAR. We propose to develop a strategy that makes T lymphocytes carrying CAR insensible to the blocking effect of the tumor. We believe that with this strategy, we will be able to give the patient T lymphocytes that are more potent and possibly eliminate the tumor.
We have constructed one of this CAR and found that they can kill the majority of GBM tumor cells, but some of the tumor cells are capable to block the T lymphocytes that carry this CAR. We have identified how the tumor cells are blocking the T lymphocytes carrying the CAR. We have now identified in vitro the best strategy to block this effect, and we are now planning to define in an in vivo model if this strategy allows the tumor eradication.