Boosting CAR-T cells for improved cancer immunotherapy

Chimeric antigen receptor (CAR) T cell therapy is approved for blood cancers while for solid tumors, including glioblastoma, the therapy is faced with hurdles.

These include poor CAR-T cell migration across tumor vessels into the tumor bed, local immunosuppression that dampens the potency of CAR-T cells, and antigen heterogeneity that obstructs effective targeting of all tumor cells within a tumor, leading to “antigen-escape” and regrowth of tumors that no longer respond to the therapy.

We have developed CAR-T cells against the glioblastoma-associated antigen IL13Rα2.

The CAR-T cells will be armed with i) recombinant “attachin” to adhere to activated integrins on tumor endothelial cells; ii) secretion of the TNF ligand LIGHT to induce antigen-presenting niches within the tumor for activation of immune cells; and iii) secretion of proinflammatory neutrophil-activating protein (NAP) to activate endogenous T cells to target individual tumor-specific antigens, leading to killing of tumor cells independently on whether they express IL13Rα2 or not.

The applied approaches are based on state-of-the-art knowledge on immunity in the central nervous system, immune cell transmigration across tumor endothelial cells, antigen-presenting niches, immunological mechanisms behind epitope spread and advanced CAR-T cell design.The overall goal is to make CAR-T cell therapy effective against glioblastoma and offer a new therapeutic option to patients for whom no hope exists today.