71 - An in silico designed dosimetric autologous living vaccine consisting of with Multiple Wilms' Tumor 1 WT1-ConSynthetic–Restricted Peptide mimotopic Epitopes RMFPNAPYLP pulsed dendritic cells on a personalized Active Network analysis for asymptomatic or minimally symptomatic metastatic Pancreatic Cancer

Abstract

First described in the 1970s, dendritic cells (DC) are currently subjects of intense investigation to exploit their unique antigen-presenting and immunoregulatory capacities. In cancer, DC show promise to elicit or amplify immune responses directed against cancer cells by activating natural killer (NK) cells and tumor antigen-specific T cells. Wilms' tumor 1 (WT1) protein is a tumor-associated antigen that is expressed in a majority of cancer types and has been designated as an antigen of major interest to be targeted in clinical cancer immunotherapy trials. DendriGeneaTM®-PAC is an in silica designed dosimetric dose calculated autologous living vaccine consisting of with Multiple Wilms' Tumor 1 WT1-ConSynthetic–Restricted Peptide mimotopic Epitopes RMFPNAPYLP pulsed dendritic cells on a personalized Active Network analysis of asymptomatic or minimally symptomatic metastatic Pancreatic Cancer. In this scientific work we describe the generation, cryopreservation, and thawing of clinical grade autologous monocyte-derived DC vaccines that are loaded with WT1 by messenger RNA (mRNA) electroporation. This in-house-developed transfection method gives rise to presentation of multiple antigen epitopes and can be used for all patients without restriction of human leukocyte antigen (HLA) type. We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV) on an artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS).