The goal of the PB003 project is to develop a bimodal fusion protein (BFP), whereby an NK cell-activating ligand is fused to an antibody (immunoglobulin), which in turn recognizes and binds to protein targets found on the surface of cancer cells. The resulting BFP will activate NK cells in the tumor microenvironment and simultaneously enhance immune system activity by reducing Treg cell-mediated immunosuppression.
Cancer cells are able to evade immune system responses in the tumor microenvironment by inducing immunosuppression through a variety of mechanisms. Therefore, immunotherapy aims to restore the ability of immune cells to fight cancer by inhibiting immunosuppression and also by activating, among others, NK cells. Natural Killer (NK) cells are capable of directly targeting and killing cancer cells. They play a key role in triggering an adaptive immune response. Enhancing NK cell function in the context of cancer is therefore a promising route for immunotherapy.
The PB003 project focuses on cancer immunotherapy via the intertwined immunosuppressive pathway between NK and Treg cells. The therapeutic strategy being developed aims to strengthen and direct a patient’s natural immune response against malignant cells, thereby targeting diseased tissue while minimizing impact on healthy tissue. The target indication will be a subtype of lung cancer, specifically Non-Small Cell Lung Cancer (NSCLC).
Lung cancer is a leading cause of cancer mortality and the second most common cancer diagnosed worldwide. The overall five-year survival rate ranges from 10% to 20%. Factors influencing the development of lung cancer include smoking, frequent contact with asbestos, various metals, organic chemicals, radiation, pollution, and dietary factors. Carriers of the human immunodeficiency virus (HIV), the human papillomavirus (HPV), and patients with a history of tuberculosis are also believed to be at higher risk of developing lung cancer.
Pure Biologics has validated the dozens of antibodies that were selected in vitro for two protein targets, including recombinant proteins as well as live cells expressing these target antigens. Further selections are ongoing. Optimal conditions for an NK cell activation assay using an immunoligand were developed and several model variants for BBF protein were obtained. They will be tested in functional assays.
PROJECT DATA SHEET
Title: Development of an immunoligand-based therapy harnessing the immune system to fight cancer
Program: Smart Growth Operational Programme for 2014-2020
Value: PLN 39 905 405.00
Contribution of European Funds: PLN 30 130 439.00
Start: 1st February 2019
End: 31st December 2023