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Recruitment of CD103+ dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy

Sci Adv. 2019-12; 
Williford JM, Ishihara J, Ishihara A, Mansurov A, Hosseinchi P, Marchell TM, Potin L, Swartz MA, Hubbell JA.
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Gene Synthesis The sequence encoding for the fusion of human VWF A3 domain residues Cys1670-Gly1874 (907 to 1111 of mature VWF), a (GGGS)2 linker, and murine CCL4 was synthesized and cloned into the pcDNA3.1(+) cytomegalovirus-driven mammalian expression vector by GenScript. Get A Quote

摘要

Although a clinical breakthrough for cancer treatment, it remains that a minority of patients respond to checkpoint inhibitor (CPI) immunotherapy. The composition of tumor-infiltrating immune cells has been identified as a key factor influencing CPI therapy success. Thus, enhancing tumor immune cell infiltration is a critical challenge. A lack of the chemokine CCL4 within the tumor microenvironment leads to the absence of CD103+ dendritic cells (DCs), a crucial cell population influencing CPI responsiveness. Here, we use a tumor stroma-targeting approach to deliver CCL4; by generating a fusion protein of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor, we show that CBD fusion enhances CCL4 t... More

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