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

Project Details

Description

Breast cancer (BC) is a leading cause of female death worldwide. In particular, the BC subtype characterized by high expression of the humans epidermal growth factor receptor 2 (HER2) tends to be more aggressive than offer BC types. the HER2 BC subtype represents 15-20% of all BC's. Although HER2-targeted therapy significantly improved the prognosis of HER2 BC patients, HER2 metastatic BC remains difficult to cure due to primary or acquired therapy resistance. Therefore, development of new approaches is key to improve the treatment outcome of HER2 BC. in the ARG-project, we will studi in vivo chimeric antigen receptor engineered T (CAR-T) cells as a therapy for HER2 BC. CAR-T cells have achieved unprecedented success in hematological malignancies. In order to mirror the success in solid tumors such as HER2 BC, it is top priority to develop an effective CAT-T cell therapy that can be easily upscaled and that is affordable. To that end it is of utmost importance to improve the design of the CAR as well as the armor of the T cell, and to simplify the CAR-T cell manufacturing process. in the ARG-project we will work on these aspects, building on innovative technologies developed at the Vrije Universiteit Brussel, in particular nanobodies (NBS) to develop T cell-targeted NB-displaying lentiviral vectors (LV's), that encode NB-engineered Cars (NanaCars) and when required, factors enhance T cell homing, tumor infiltration and functionality. We will study LVs displaying cross reactive CD3, CD4, or CD8-specific NBS that harbor T cell enhancing factors in addition to nanoCARs directed against HER2. We will study these LVs using BC 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.
Acronymani257
StatusActive
Effective start/end date1/11/2031/10/21

Keywords

  • Breast cancer

Flemish discipline codes

  • Medical imaging and therapy not elsewhere classified