CARGO: advancing chimeric antigen receptor T cell therapy using nanobody-displaying lentiviral vectors

Research into adoptive T cell therapy for cancer is trending. Herein, the focus lies on chimeric antigen receptor engineered T (CAR-T) cells as evidenced by over 100 companies investing in CAR-T cell technology. This is explained by the success achieved by CAR-T cells in hematological malignancies.
However, similar results have not been obtained in the context of solid tumors. Among the top priorities to develop an affordable and effective CAR-T cell therapy for solid tumors is simplifying the CAR-T cell manufacturing process and improving the design of the CAR as well as the armor of the T cell. In the CARGO-project, we will work on these aspects, building on innovative technologies developed at the VUB, in particular nanobodies (Nbs), to develop T cell-targeted Nb-displaying lentiviral vectors (LVs) harboring Nb-engineered CARs (nanoCARs) and when required factors that enhance T cell homing, tumor infiltration and functionality.
We will study LVs displaying cross-reactive CD3-, CD4- or CD8-targeted Nbs that harbor T cell enhancing factors in addition to nanoCARs directed against HER2.

We will study these LVs using breast cancer spheroids generated with HER2+ cells of human or mouse origin as well as in immunocompetent mouse models. The latter will provide an in-depth preclinical analysis of the potential of the in vivo nanoCAR-T cell approach, and as such will open the path to clinical translation.