Luis A Rojas, Zachary Sethna, Kevin C Soares, Cristina Olcese, Nan Pang, Erin Patterson, Jayon Lihm, Nicholas Ceglia, Pablo Guasp, Alexander Chu, Rebecca Yu, Adrienne Kaya Chandra, Theresa Waters, Jennifer Ruan, Masataka Amisaki, Abderezak Zebboudj, Zagaa Odgerel, George Payne, Evelyna Derhovanessian, Felicitas Müller, Ina Rhee, Mahesh Yadav, Anton Dobrin, Michel Sadelain, Marta Łuksza, Noah Cohen, Laura Tang, Olca Basturk, Mithat Gönen, Seth Katz, Richard Kinh Do, Andrew S Epstein, Parisa Momtaz, Wungki Park, Ryan Sugarman, Anna M Varghese, Elizabeth Won, Avni Desai, Alice C Wei, Michael I D'Angelica, T Peter Kingham, Ira Mellman, Taha Merghoub, Jedd D Wolchok, Ugur Sahin, Özlem Türeci, Benjamin D Greenbaum, William R Jarnagin, Jeffrey Drebin, Eileen M O'Reilly, Vinod P Balachandran
Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1 , yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3 . Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin)...
June 2023: Nature