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Adding combination immunotherapy consisting of cancer vaccine, anti-PD-1 and anti-CSF1R antibodies to gemcitabine improves anti-tumor efficacy in murine model of pancreatic ductal adenocarcinoma

  
@article{APC5117,
	author = {May Tun Saung and Lei Zheng},
	title = {Adding combination immunotherapy consisting of cancer vaccine, anti-PD-1 and anti-CSF1R antibodies to gemcitabine improves anti-tumor efficacy in murine model of pancreatic ductal adenocarcinoma},
	journal = {Annals of Pancreatic Cancer},
	volume = {2},
	number = {0},
	year = {2019},
	keywords = {},
	abstract = {Background: Immunotherapy can take advantage of the immunogenic response that chemotherapy elicits in tumors. Gemcitabine is a standard agent used in the treatment of pancreatic cancer, with known effects on the tumor immune microenvironment. The combination immunotherapy of the GVAX cancer vaccine, anti-PD-1 antibody and anti-CSF-1R antibody has been shown to improve survival in a murine model of metastatic pancreatic adenocarcinoma. This combination regimen also increased the infiltration of CD8+ T-cells that expressed both PD1 and CD137, and these T-cells were shown to express high levels of interferon-gamma, a marker of cytotoxic effector CD8+ T-cells. The effect of the addition of gemcitabine to this promising immunotherapy regimen has not been investigated. 
Methods: Mice with liver-metastatic pancreatic adenocarcinoma were followed for 120 days to determine if adding immunotherapy, which comprised of varying combinations of GVAX, anti-PD-1 antibody and anti-CSF-1R antibody, to gemcitabine improved survival. Tumor-infiltrating CD8+ T-cells and myeloid cells, harvested after the mice were treated for 2 weeks, were analyzed with flow cytometry to characterize the effect the chemo-immunotherapy regimen had on the tumor microenvironment (TME).
Results: Adding combination immunotherapy after gemcitabine improved survival compared to gemcitabine treatment alone (gemcitabine/GVAX/anti-PD1, P},
	issn = {2616-2741},	url = {https://apc.amegroups.org/article/view/5117}
}