Synergy between oxaliplatin and adenovirus initiates immunogenic cell death in human colorectal carcinoma cells

Abstract Externalization of Calreticulin (CALR) is the critical first step in initiation Immunogenic Cell Death. Since Oxaliplatin (OX) cooperates with an oncolytic chimeric human adenovirus Ad5/3-NP2.ADP (ADP) to induce adaptive immunity as well regression established cancer, we sought determine whether cooperation was additive or synergistic. Methods include immunohistochemistry (IHC) for expression mice 11 days after intratumoral injection OX-ADP mixture. In vitro assays limiting dilutions OX and ADP on Clone A colorectal carcinoma cell monolayers were cultured 3 cytotoxicity, viral infectivity by GFP, externalized CALR (ectoCALR) cells measured static cytometry. Synergy using SynergyFinder 3.0 (Ianevski et al., PMC9252834) that creates 2-D interactive surfaces measure synergy antagonism. Areas have mean scores > 10. IHC revealed strong treated tumors, weak tumors injected alone minimal PBS controls. Mean Viral Infectivity score 27.2 area (Ox μM, MOI): (0.12μM, 4 MOI) (12.5μM, 100 while ectoCALR 29.2 OX/ADP (0.01μM, 0.16) 20 MOI). The role oxidative endoplasmic reticulum stress basis under study. are synergistic their ability initiate ICD which important vaccine development.