PB004 PureBIKE

Triple-negative breast cancer (TNBC) is a highly proliferative, rapidly growing, and aggressive form of cancer. TNBC can be further categorized into three types: Type 1 (also known as the “cold” type) is characterized by a tumor with low infiltration of immune cells into the tumor microenvironment; Type 2 is characterized by inactive cells of the innate immune system; Type 3 (also known as the “hot” type) is characterized by an immune system response that remains undisturbed. The aim of the PB004 (PureBIKE) project is to develop bispecific antibodies that convert a ‘cold’ TNBC tumor into a ‘hot’ tumor, rendering it more visible to the immune system.

OBJECTIVES

The goal of the PB004 project is to develop a Bispecific Killer Engager (BIKE), an antibody designed as an immunotherapeutic drug candidate for use in therapy of triple-negative breast cancer (TNBC). The strategy behind the BIKE antibody is to facilitate contact of a cancer cell with an immune system effector known as a Natural Killer (NK) cell, thereby activating the NK cell and triggering destruction of the cancer cells.

DESCRIPTION

TNBC is a highly aggressive form of breast cancer. It is associated with large tumor size and a high degree of malignancy with frequent metastases. The current five-year survival rate remains only fourteen percent. TNBC cells are characterized by increased production of specific surface proteins that are essential for tumor proliferation and resistance to chemotherapy.

In the tumor microenvironment, immune system activity is suppressed (immunosuppression) and among others, the activities of NK cells are inhibited. Under normal conditions, activation of NK cells is mediated via a specific set of cell surface receptors. Once activated, NK cells secrete macromolecules into the tumour microenvironment, which attack and destroy targeted cancer cells.

The PB004 project aims to develop a BIKE antibody, which will incorporate two functions, each working in a different manner. The first function will be to recognize and selectively bind to TNBC tumor cells via their unique surface receptors. The second function will be to specifically bind and activate NK cells. Through the activity of the BIKE antibody, NK cells will become simultaneously activated and brought into close proximity to the tumor cell surface, thereby facilitating tumor destruction.

PROJECT PROGRESS

Pure Biologics successfully carried out over a dozen selections, which resulted in obtaining candidates for antibodies against two molecular targets. These molecules were produced and tested according to their binding specificity to antigens. Currently, protein variants are being prepared for the bispecific antibody BIKE for selection of the most efficiently produced one and characterized by best properties. The bispecific BIKE molecules will be then subjected to activity and cytotoxicity tests.

PROJECT DATA SHEET

Title: Development of a bispecific antibody fragment for simultaneous cancer control and immune cell recruitment
Program: Smart Growth Operational Programme 2014-2020
Value: PLN 38 617 125,00
Contribution of European Funds: PLN 28 789 080,00
Start: 1^st July 2019
End: 31^st December 2023