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Project
CARGO: advancing chimeric antigen receptor T cell therapy using nanobody-displaying lentiviral vectors (FWOSB101)
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.
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.
Date:1 Nov 2020 → Today
Keywords:Cancer, T cell therapy, Nanobody-display technology
Disciplines:Adaptive immunology, Applied immunology, Cancer therapy