Determination of binding characteristics and cytotoxic activity of bispecific T cell engagers
T cell-based cancer immunotherapies have revolutionised cancer treatment by targeting and mobilising T cells to eradicate malignant cells.
Based on their mechanisms of action, T cell-based cancer immunotherapies can be mainly divided into two classes: the first targets immunosuppressive factors, represented by immune checkpoint inhibitors (e.g. PD-1, PD-L1, and CTLA-4 based therapies); the second focuses on immune-stimulatory pathways, represented by chimeric antigen receptor (CAR) T cells and bispecific T cell engagers (BiTE or TCE). Bispecific T cell engagers are antibodies that bind to two different targets: they simultanously bind to tumour-associated antigens (TAA) and CD3 subunits on T cells. This simultaneous binding results in the recruitment and cross-linking of cytotoxic T cells and cancer cells. These cross-linked T cells are then activated and start to proliferate, leading to the formation of the immunologic synapse. Activated T cells secrete cytokines like perforins and granzymes, resulting in the cytotoxic lysis of target cells.
Different formats are classified as fragment-based (without an Fc domain) and asymmetric or symmetric Fc-bearing molecules. The molecules may contain mutations that affect chain pairing, other manufacturability parameters, Fc-mediated effector
functions, and half-life.
Characterisation and quality control of this class of products are critical and require the use of innovative technologies. In this application note, bispecific T cell engagers (TCE) were generated using GlycoConnect® technology.
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1 Quality Assistance S.A., Technoparc de Thudinie 2, 6536 Donstiennes, Belgium
2 Synaffix - A Lonza Company, Kloosterstraat 9, 5349 AB Oss, The Netherlands
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