A first-in-class, humanized antibody targeting alternatively spliced tissue factor: preclinical evaluation in an orthotopic model of pancreatic ductal adenocarcinoma

RNA sequencing of 9 samples (3 per group) generated 30 million 150 base long paired end reads revealed differential isoform expression of about 1100 gene transcripts. Hg19 was used as a reference genome for alignment, transcriptome index was created in kallisto using Ensembl cDNA sequences for the reference genome. This index was then used to quantify transcript abundance in raw counts and transcript per million (TPM). We report a suppression in the expression of genes associated with cell cycle regulation (most strongly HBGEF, STN1, ECT2, PLCD3, and RHOC). Suppression of HBGEF and STN1 in hRabMab1 treated tumors was validated by qRT-PCR. Systemic delivery of a humanized monoclonal antibody targeting human alternatively spliced tissue factor (asTF): asTF-targeting hRabMab1 antibody treatment compared to vehicle or hIgG1 controls in nude mice after orthotopic injection of human Pt45.P1 pancreatic ductal adenocarcinoma cells. RNA was isolated from crushed tumors representing the median 3 tumor volumes from each treatment group (Vehicle, hIgG1, hRabMab1). RNA library preparation, next generation sequencing, and sequence alignment were performed by the CCHMC DNA Sequencing and Genotyping Core, Cincinnati, Ohio.