Novel Targeted Immunotherapy for CML Blast Cells

摘要

An emerging problem in chronic phase CML is molecular persistence. It is mainly due to the quiescent stem cell population that are completely insensitive to Imitinib therapy. We have developed a novel immunotherapy against CML. We have screened One-Bead-One-Compound (OBOC) combinatorial libraries and identified cyclic peptide ligands that are bind CML cancer cells. These ligands will then be ligated to the N-termini of the engineered Fc fragment of human immunoglobulin in a site-specific manner. We hypothesize that these cancer targeting ligand-Fc fragment conjugate (we call it 'ligand-body') will bind to CML cells via the peptide or peptidomimetic ligand domain and the Fc immunoglobulin domain will be used to harness the anti-cancer innate immunity against CML cells in vivo. The innate immune system includes immune effector cells such as NK cells NKT cells macrophages and leukocytes and complement system. As mentioned in Aim 1 and Aim 2 we have modified Fc domain for specific N-terminal ligation and produced modified protein for Ligand-body production. In the second year functional characterization for the ligand-body will be performed.