Our immune system is composed of two arms: antibodies and T cells.

Soluble antibody molecules can bind to cell surface expressed proteins with high affinity and specificity. Upon binding, they can recruit effector cells of the immune system such as macrophages and Natural Killer (NK) cells, or mediate a biological signal into cells. Antibodies constitute today the most important class of targeted therapeutics in the bio-pharmaceutical industry. HOWEVER, analysis of the human proteome reveals that only 20% of human proteins are expressed on the cell surface. The remaining 80% of the human proteome is intracellular, and is therefore not accessible by conventional antibodies for therapeutic targeting clinical applications. Thus, there is an urgent need for the development of novel therapeutic antibodies against these intracellular based targets.

T cells mediate cellular immunity. CD8+ Cytotoxic T cells (CTLs) are the most potent effector cells of the immune system because they can recognize and kill diseased cells in a highly specific manner. They recognize intracellular proteins due to their ability to bind to the cell surface-expressed MHC-peptide complex, which presents peptides derived from intracellular proteins. Upon specific recognition of the MHC-peptide complex by the T-cell receptor (TCR), the CTLs undergo activation, proliferation and expansion, leading to destruction of the target diseased cells. HOWEVER, T cells are very difficult to manipulate for therapeutic applications and thus their advantage in recognizing intracellular targets is very difficult to apply for clinical therapeutic purposes.





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