Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses
Alexander Ling, Jennifer Gantchev, Michael C. Prabhu, Sreyashi Basu, Ryuhjin Ahn, Alicia D. D’Souza, Nafisa Masud, Anna Ball, Odysseas Nikas, Genaro R. Villa, Michael S. Regan, Gerard Baquer, Georges Ayoub, Charles A. Whittaker, Zaki Abou-Mrad, Andres Santos, Charles Couturier, Dina ElHarouni, Jayne Vogelzang, Kenny Yu, Hong Chen, Zhong He, Wen Jiang, Calixto‐Hope G. Lucas, Haley E. Sax, Frederick F. Lang, Vinay K. Puduvalli, Viviane Tabar, Cameron Brennan, Adrienne Boire, Matthias Holdhoff, Chetan Bettegowda, Michael J. Cima, Isaac H. Solomon, Ying Yuan, Paul P. Tak, Accelerating GBM Therapies TeamLab, Padmanee Sharma, Forest M. White, Keith L. Ligon, Nathalie Y.R. Agar, David A. Reardon, Giacomo Oliveira, E. Antonio Chiocca, Jennifer Wiley, Kathryn Partridge, Rameen Beroukhim, Amanda Spearman, Ugonma Chukwueke, Patrick Y. Wen, A. Chiocca, Sarah Frisken, Brian J. Coyne, Daniel Triggs, Kimberly L. Vasquez, Michal O. Nowicki, Himanshu Soni, Raziye Piranlioglu, Marco Mineo, Ana Montalvo Landivar, Sylwia A. Stopka, Md Amin Hossain, Seth Malinowski, Sonam Bhatia, Thomas P. Quinn, Marla J. Polk, Alexsandra Espejo, Jingjing Sun, Yulong Chen, Sonali Jindal, Jason T. Huse, Lisa Norberg, Sangeeta Goswami, Betty Y. Kim, Kadir C. Akdemir, Brittany C. Parker Kerrigan, Douglas Nielsen, Jian Hu, Pratibha Sharma, Chetna Wathoo, Gregory M. Buchold, Jiyong Liang, Stuart S. Levine, Qun Cao, Alexei Stortchevoi, Shahiba Ogilvie, Alexandra Giantini-Larsen, Kelsey Hopland, Yuval Elhanati, Rachel Estrera, Isaiah Osei-Gyening, Tejus Bale, Christopher Douville, Jordina Rincon Torroella, Vasilena Gocheva, Francesca Barone, Jennifer Moliterno
Abstract
Recurrent glioblastoma (rGBM) remains incurable. One barrier to the development of effective rGBM therapies is the difficulty in collecting posttreatment tumor tissue. Serial multiomic assays from longitudinal rGBM biopsies may uncover tumor responses to a treatment. Here, we obtained 97 serial rGBM biopsy cores over 4 months from the first two patients participating in a clinical trial of repeated intratumoral dosing of the immunotherapeutic agent CAN-3110. Multiomic analysis of the biopsy cores revealed therapeutic effects, including longitudinal and spatial reshaping of the rGBM's microenvironment, expansion of new T cell tissue-resident effector memory clonotypes against CAN-3110 epitopes and other undetermined antigens, and expression of human leukocyte antigen (HLA)-presented immunopeptides, including cancer testis antigens. Moreover, serial integrated multimodal analyses provided evidence of therapeutic responses to CAN-3110 despite traditional magnetic resonance imaging indicating progression. Clinically, the two treated patients achieved a pathologic response or stable clinical disease, respectively. These results show the value of longitudinal tissue sampling to understand rGBM's evolution during administration of an investigational therapy.