O-OGC07 Endoscopically derived oesophageal adenocarcinoma organoids to assess potential response to neo-adjuvant therapy and virotherapy

Background Organoids are 3D models that retain the architecture and function of the organ from which they are derived. Culture of oesophageal adenocarcinoma organoids from individual’s standard endoscopic biopsies to assess response to therapy could dramatically alter the neo-adjuvant treatment paradigm, giving clarity over who will benefit from therapy, including novel treatment methodologies. Immune checkpoint blockade (ICB) has been shown to be effective in oesophageal adenocarcinoma. Combining Oncolytic Virotherapy with ICB could enhance the action of ICB alone, through selective infection of tumour cells accompanied by immunogenic cell death, with release of neo-tumour antigens and alteration of the tumour microenvironment. Methods This study uses organoids derived from endoscopic biopsies to assess the viability of an oncolytic herpes simplex virus in the treatment of oesophageal adenocarcinoma. Samples were taken at staging endoscopy using standard biopsy forceps. Tissue specimens were dissociated using the Miltenyi tumour dissociation kit before being suspended in Matrigel in conditioned media. Media was changed every 48 hours with domes being split every 7-10 days. After >6 passages organoids were incubated with an oncolytic herpes simplex virus lacking ICP 34.5 and 47. Growth was monitored, and green fluorescence protein expression measured using the Incucyte SX5 Live Cell Analysis system. Results Organoids were successfully established and cultured beyond 6 passages for patients with oesophageal adenocarcinoma. Organoids incubated with an oncolytic herpes simplex virus demonstrated significantly reduced growth compared to untreated organoids with increased expression of green fluorescence protein indicating viral infection. Conclusions We have demonstrated a successful methodology to culture Oesophageal adenocarcinoma organoids from endoscopic biopsies. Further work to determine their responses to standard chemotherapy used in the perioperative phase will help to assess their potential for providing bespoke therapy in the future. Oncolytic herpes simplex virus is able to infect and cause lysis of OAC organoids supporting its potential use in driving an increased inflammatory tumour microenvironment which could be combined with immune checkpoint blockade to induce durable responses for patients.