(188cb) Selective Targeting of Acute Lymphoblastic Leukemia (ALL) Via CD22 Targeting Liposomal Nanoparticles

Leukemia is a type of blood cancer caused by the increased number of abnormal white blood cells that is detrimental to cause death for many patients. The severity of leukemia has been rising, and the mortality rate in the patients is significant today. Regarding this severity, several first-line treatments have been developed, such as imatinib mesylate. However, these treatments induce numerous side effects, such as severe deficiency in blood cell counts because not only they target leukemia cells but also healthy cells as well. Therefore, it is critical to develop therapeutics that only target leukemia cells to reduce systematic toxicity in patients. Here, we demonstrate rationally engineered multifunctional liposome model developed from our lab that presents leukemia cell specific targeting ligands on its surface to selectively target leukemia cells over healthy cells. Among the many types of leukemia, we specifically focused on acute lymphoblastic leukemia (ALL) which is the most common type of leukemia among the children in the United States. Throughout numerous studies in the past, CD22 has been validated as a potential target for B-cell ALL and after analyzing the 3D crystal structure (PDB ID : 5VL3) of the interaction between CD22 and its therapeutic antibody, Epratuzumab, we isolated potential CD22 binding peptide sequence. Utilizing this short peptide and presenting on liposome platform, we performed cellular uptake assays on two different cell lines, Raji (CD22+) and Jurkat (CD22-). The results showed significant uptake in Raji starting at 4% peptide density comparing to Jurkat. Furthermore, the peptide was determined to be specific as the result of competitive-binding assay. In spite of the selectivity on CD22, there still need numerous improvements and modifications on our model to enhance further selectivity. Regarding this purpose, we are going to investigate another receptors that could be potentially dual-targeted with CD22 to achieve synergistic effects to further selectively target leukemia cells. Altogether, this model will potentially enable the disease driven engineering of a nanoparticle-based drug delivery system in the treatment of leukemia.