Based on the current literature and to maximize engineering efficiency of treatment, the researchers plan on engineering two liposomes to successfully eliminate all PaCSCs throughout the body. One liposome will encompass the metabolic treatments and include phenformin (OXPHOS inhibitor), devimistat (Krebs cycle inhibitor), RRx-001 (c-Myc inhibitor), auranofin (glycolysis inhibitor), and ONC201 (Akt/ERK inhibitor, TRAIL regulator). The second liposome will encompass the self-renewal treatments and include navicixizumab (bispecific antibody for VEGFR and DLL4 in Notch), a bispecific antibody for VEGFR and JAG2 in Notch, vantictumab (frizzled receptor inhibitor), PRI-724 (β-catenin inhibitor), LGK974 (small molecule porcupine inhibitor), ETC-159 (small molecule porcupine inhibitor), BMS-833923 (smoothened inhibitor), and PF-0444913 (smoothened inhibitor). Both liposomes will be decorated with PaCSC specific antibodies that bind to PaCSC specific antigens cluster of differentiation 44 (CD44), cluster of differentiation 24 (CD24), and epidermal surface antigen (ESA) to ensure targeted delivery to cancerous stem cells. Cells positive to all these antigens had a 100-fold increased tumorigenic potential compared to non-tumorigenic pancreatic cancer cells (Lee et al. 2016). The researchers will therefore incorporate three monoclonal antibodies, one for each of these antigens, into the membranes of the two liposomes.
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