Our purpose is to isolate nanobodies that bind cancer stemm cells and have a direct cytotoxic effect on them, or could act as carriers of cytotoxic drugs specifically towards them.
Start – End dates: 01/09/20 – 31/08/23
Project reference: Retos Colaboración 2019 (RTC2019-006809-1)
Total budget: 940,000€
Financed by: State Research Agency under the Ministry of Science and Innovation, Spain
¨Funded by the State Research Agency under the Ministry of Science, Innovation and Universities; program Retos Colaboracion 2019, project reference: RTC2019-006809-1¨
Partners: Vall d’Hebron Research Institute (VHIR) (Barcelona, Spain)
Summary:
The NanoDIRE-CT project focuses on the search for therapies aimed at cancer stem cells (CSCs) based on the use of nanobodies, which are antibody fragments characterized by their small size, stability and low immunogenicity. These physico-chemical characteristics make them ideal molecules to bind to hard-to-reach tumors and cells with metastatic potential. Our purpose is to isolate nanobodies that bind CSCs and have a direct cytotoxic effect on them (therapeutic nanobodies) or could act as carriers of cytotoxic drugs specifically towards them (nanocarriers). The ability of these nanobodies to detect CSCs in the blood of patients could be exploited to alert on the appearance of circulating tumor cells and risk of metastasis (diagnostic nanobodies).
From a technological point of view, an important aspect to highlight is the use of different complementary preclinical models that will allow a reduction of costs and times, together with a greater biological robustness. We will begin with the validation of 25 clones of nanobodies previously isolated based on their affinity for CSCs. The antitumor efficacy of these nanobodies will be tested in CSC cultures for two types of cancer that have unmet clinical needs: breast cancer and pancreatic cancer. In vitro results will be validated in vivo using an innovative xenotransplant system in zebrafish larvae. This animal model is still recent in the industry, but its value has already been proven in the study of different diseases and the discovery of new drugs. Its small size, high number of progeny, low cost of housing and high genetic and physiological homology with humans make it a biologically valid and predictive model. Thanks to its use, the selection of nanobodies identified in vitro will be refined to increase the chances of success in the successive test in murine models. Finally, access to patient samples will allow us to extend the therapeutic applications of nanobodies to the diagnostic field.