Project description:For the subcutaneous model, 5x105 KPC-Luc cells were injected subcutaneously near the right flank of female C57BL/6 mice. 6-7 days after tumor implantation mice were randomized into 4 treatment groups and treatedwith VIP-R antagonist and/or anti-PD-1. While scram+IgG control mice received scrambled peptide and isotype IgG, the VIP-R antagonist, anti-PD-1 and VIP-R antagonist and anti-PD-1 groups received VIP-R antagonist and IgG; scrambled peptide and anti-PD-1; and VIP-R antagonist and anti-PD-1, respectively. The treatment regimen involved administering 10μg of scrambled or VIP-R antagonist: ANT008, subcutaneously every day and 200μg of IgG or anti-PD-1 intraperitoneally once every three days, for a total of 10 days.
Project description:For the subcutaneous model, 5x105 KPC-Luc cells were injected subcutaneously near the right flank of female C57BL/6 mice. For the MT5 or Panc02 models, 5x105 were injected subcutaneously near the right flank of female C57BL/6 mice. For the orthotopic KPC-Luc model, mice were anesthetized, and the KPC-Luc cells were suspended in Matrigel and injected in the tail of the pancreas following laparotomy. 6-7 days after tumor implantation mice were randomized into 4 treatment groups and treatedwith VIP-R antagonist and/or anti-PD-1. While scram+IgG control mice received scrambled peptide and isotype IgG, the VIP-R antagonist, anti-PD-1 and VIP-R antagonist and anti-PD-1 groups received VIP-R antagonist and IgG; scrambled peptide and anti-PD-1; and VIP-R antagonist and anti-PD-1, respectively. The treatment regimen involved administering 10μg of scrambled or VIP-R antagonist: ANT008 or ANT308, subcutaneously every day and 200μg of IgG or anti-PD-1 intraperitoneally once every three days, for a total of 10 days.
Project description:Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients.
Project description:Goal: determine how transcriptome of immune cells within the tumor microenvironment changes as a function of CD40 agonist and/or immune checkpoint blockade (anti-PD-1 AND anti-CTLA-4; "ICB") therapy
Project description:In our study, we aimed to investigate adaptive processes of tumors under treatment and therefore, generated PDAC patient-derived organoids (PDOs) and 2D cell lines before and after chemotherapy. We enrolled a patient with borderline resectable PDAC who received neoadjuvant FOLFIRINOX. Endoscopic fine needle (pre-FFX) and surgical biopsies (post-FFX) were used to generate PDOs and 2D cells. Whole exome sequencing (WES) and RNA sequencing data of the pre-FFX and post-FFX organoids were compared in order to evaluate the genetic landscape and PDAC subtypes. Although transcriptional subtyping classified both PDOs as classical PDAC, gene set enrichment analysis (GSEA) revealed a reduced pathway activation linked to the basal-like phenotype such as KRAS signaling in the post-FFX organoids. WES did not show major differences in the genetic landscape of the tumor pre- and post-FFX induction suggesting a plasticity process rather than a clonal selection during chemotherapy. 2D cells were subjected to an unbiased automated drug screening of 415 compounds to investigate FFX-induced vulnerabilities. Top targets such as MEK inhibitors were validated manually in the 2D cells and organoids and an increased sensitivity was observed in the post-FFX cells. Thus, integrating functional layers into personalized medicine allows to identify chemotherapy-induced vulnerabilities as potent targeted therapy options in PDAC.
Project description:TGFbeta promotes the bypass of KRAS* dependency in PDAC. To dissect the molecular mechanisms that regulated by TGFbeta in PDAC cells, we conducted RNA-seq analysis of iKPC PDAC cells with or without TGFbeta treatment.