This project is game-changing because it proposes a novel approach to make immunotherapies effective against GBM. By genetically restoring T cell functionality and freeing them from the bone marrow in mice models, the researchers have observed that genetically altered mice can reject GBM and may survive long-term when administered immunotherapies that previously did not work. The project also involves the development of a new class of drug with the help of a Nobel Laureate and a group of medicinal chemists. This drug is anticipated to enhance the success of immunotherapies against GBM by restoring T cell number and function.

This project can help patients with brain cancer by potentially making immunotherapies effective against GBM. The new class of drug being developed could restore the number and function of T cells, enhancing the body’s immune response against the tumour. This could lead to improved survival rates and quality of life for patients with GBM and potentially other types of cancer that infiltrate the brain.

This grant is aimed at deriving pharmacologic reversal of T cell sequestration and restoration of T cell function in an effort to license immunotherapeutic success against GBM. The Fecci Lab have previously identified that T cells are sequestered in the bone marrow of patients with intracranial tumours, due to loss of the S1P1 receptor from the T cell surface. They have genetically shown that when S1P1 is restored in mice models, these mice reject GBM and may survive long-term when administered immunotherapies that did not previously work. To translate their findings, they have discovered that a compound that can prevent the loss of S1P1, restoring T- cell function. While this compound works exceedingly well outside the body, it is currently too unstable in the body to be useful as a drug. The Fecci lab has teamed up with a local non-profit group of medicinal chemists from RTI whose expertise is in modifying compounds to make them into useable drugs. This grant proposal aims to take this discovery and invent an entirely new class of drug that they anticipate will newly license immunotherapies success against GBM by restoring T cell number and function.