TGFß blockade in pancreatic cancer enhances sensitivity to combination chemotherapy

We evaluated the TGFß blocking antibody NIS793 in combination with either gemcitabine/n(ab)-paclitaxel or FOLFIRINOX chemotherapy in orthotopic pancreatic cancer. Blockade of TGFß with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. TGFß blockade decreased total aSMA+ fibroblasts but had minimal effect on fibroblast heterogeneity. Overall design: 6694c2 tumor cells were inoculated orthotopically into C57BL/6 mice treated with aTGFß or Isotype, +/- GnP or FOLFIRINOX (5mg/kg oxaliplatin, 75mg/kg leucovorin, 50mg/kg irinotecan, and 75mg/kg 5-FU; dosed by i.v. at day 3 and day 6). Tumors were harvested on day 14, digested, and enriched for fibroblasts using antibodies against CD31 and CD90, followed by positive selection with magnetic beads and single cell transcriptional analysis. n = 5 tumors pooled per group.