Descripció del projecte
ONA Therapeutics is a spin-off company from IRB and ICREA that is actively developing biotherapeutic drugs to attack advanced cancer. One of the main projects in the company focuses on the selective blockade of a cell surface receptor that is involved in lipid metabolism, which has been found be a key mechanism for cancer cells to become invasive and thus initiate the metastatic spread to distant organs.
One strategy to improve the selectivity of antibody drugs is to engineer the antibody paratope to achieve its conditional activation within the tumour microenvironmet, thereby improving the pharmacokinetics, safety, and therapeutic efficacy of the drug. The Laboratory of Therapeutic Proteins at Institut Químic de Sarrià – Universtat Ramon Llull (IQS-URL) has developed versatile masking strategies that are applicable across different antibody formats and specificities.
In this project, the conditional activation strategies developed by IQS-URL will be applied to antibodies developed by ONA Therapeutics for the treatment of metastatic cancer aiming to further increase their selectivity.
The project could be divided in three parts:
1. Adaptation of the masking modification to the full-length IgG antibodies of interest. Design of suitable linkers for tumor-specific proteolytic unmasking. Validation of activity and conditional activation in vitro.
2. Optimization of manufacturability and developability properties of the antibody, including stability, off-target effects, hydrophobicity, self-association, and buffer formulation at high concentrations.
3. In vivo pharmacokinetics, distribution studies, and antitumour efficacy in suitable mouse cancer models.
