Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses
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.
Authors
- Forest M. White (ORCID: https://orcid.org/0000-0002-1545-1651)
- Paul P. Tak (ORCID: https://orcid.org/0000-0002-3532-5409)
- Calixto‐Hope G. Lucas (ORCID: https://orcid.org/0000-0002-8347-9592)
- Jennifer Moliterno (ORCID: https://orcid.org/0000-0002-6413-5874)
- Ryuhjin Ahn (ORCID: https://orcid.org/0000-0001-9788-4401)
- Hong Chen (ORCID: https://orcid.org/0000-0003-2315-0645)
- Giacomo Oliveira (ORCID: https://orcid.org/0000-0001-7435-5603)
- Nafisa Masud
- Georges Ayoub (ORCID: https://orcid.org/0000-0002-1694-6779)
- Keith Lloyd Ligon (ORCID: https://orcid.org/0000-0002-7733-600X)
- Alexander Ling (ORCID: https://orcid.org/0000-0001-6194-9875)
- Yuval Elhanati (ORCID: https://orcid.org/0000-0002-4354-8864)
- Jennifer Gantchev (ORCID: https://orcid.org/0000-0001-5236-0671)
- Gregory M. Buchold (ORCID: https://orcid.org/0000-0003-0710-7866)
- Tejus Bale (ORCID: https://orcid.org/0000-0003-3641-9287)
- Kathryn Partridge
- Lisa Norberg (ORCID: https://orcid.org/0009-0007-5741-8773)
- Patrick Yung Wen (ORCID: https://orcid.org/0000-0002-0774-7700)
- Andres Santos (ORCID: https://orcid.org/0000-0001-7250-0184)
- Kenny Kwok Hei Yu (ORCID: https://orcid.org/0000-0002-2394-4990)
- Jason T. Huse (ORCID: https://orcid.org/0000-0003-4514-0640)
- Betty Y. Kim
- Frederick F. Lang (ORCID: https://orcid.org/0000-0003-3747-873X)
- Stuart S. Levine (ORCID: https://orcid.org/0000-0001-7363-562X)
- Ana Montalvo Landivar (ORCID: https://orcid.org/0000-0002-0139-772X)
- Sonam Bhatia (ORCID: https://orcid.org/0000-0003-0302-9100)
- Kelsey Hopland
- Christopher Douville (ORCID: https://orcid.org/0000-0002-2510-4151)
- Sarah Frisken (ORCID: https://orcid.org/0000-0001-5731-5095)
- Raziye Piranlioglu (ORCID: https://orcid.org/0000-0003-2450-3887)
- Charles A. Whittaker (ORCID: https://orcid.org/0000-0002-2400-0094)
- Kadir C. Akdemir (ORCID: https://orcid.org/0000-0003-2299-2373)
- E. Antonio Chiocca (ORCID: https://orcid.org/0000-0001-5183-1670)
- Himanshu Soni (ORCID: https://orcid.org/0000-0002-4765-2968)
- Alexsandra Espejo (ORCID: https://orcid.org/0000-0002-8841-7219)
- Vinay K. Puduvalli (ORCID: https://orcid.org/0000-0001-8396-9500)
- Vasilena Gocheva
- Ying Yuan (ORCID: https://orcid.org/0000-0002-3922-9553)
- Michal O. Nowicki (ORCID: https://orcid.org/0000-0002-5807-0007)
- Rameen Beroukhim (ORCID: https://orcid.org/0000-0001-6303-3609)
- Dina ElHarouni (ORCID: https://orcid.org/0000-0003-1488-0347)
- Nathalie Y.R. Agar (ORCID: https://orcid.org/0000-0003-3149-3146)
- Alicia D. D’Souza (ORCID: https://orcid.org/0000-0001-7635-7573)
- Seth Malinowski (ORCID: https://orcid.org/0000-0001-6468-3451)
- Adrienne Ann Boire (ORCID: https://orcid.org/0000-0002-9029-1248)
- Sangeeta Goswami (ORCID: https://orcid.org/0000-0001-9201-4503)
- Jennifer Wiley
- Ugonma Nnenna Chukwueke (ORCID: https://orcid.org/0000-0003-0598-9535)
- Jian Hu (ORCID: https://orcid.org/0000-0001-6657-9826)
- Gerard Baquer (ORCID: https://orcid.org/0000-0002-4433-4972)
- Sonali Jindal (ORCID: https://orcid.org/0000-0002-3911-6815)
- David A. Reardon (ORCID: https://orcid.org/0000-0001-6674-0157)
- Michael J. Cima (ORCID: https://orcid.org/0000-0003-2379-6139)
- Sylwia A. Stopka (ORCID: https://orcid.org/0000-0003-3761-6899)
- Jayne Vogelzang (ORCID: https://orcid.org/0000-0001-8249-3600)
- Marco Mineo (ORCID: https://orcid.org/0000-0001-7608-4579)
- Kimberly S. Vasquez (ORCID: https://orcid.org/0000-0003-2511-5237)
- Shahiba Ogilvie
- Anna Ball (ORCID: https://orcid.org/0009-0000-7725-4330)
- Chetan Bettegowda (ORCID: https://orcid.org/0000-0001-9991-7123)
- Daniel Triggs
- Padmanee Sharma (ORCID: https://orcid.org/0000-0003-4658-055X)
- Pratibha Sharma (ORCID: https://orcid.org/0000-0001-7070-3025)
- Michael S. Regan (ORCID: https://orcid.org/0000-0001-5252-2829)
- Amanda Spearman
- Sreyashi Basu (ORCID: https://orcid.org/0000-0002-5028-3833)
- Francesca Barone (ORCID: https://orcid.org/0000-0002-5287-9614)
- Alexei Stortchevoi (ORCID: https://orcid.org/0000-0001-9916-4344)
- Brittany C. Parker Kerrigan (ORCID: https://orcid.org/0009-0005-9268-0342)
- Viviane Tabar (ORCID: https://orcid.org/0000-0002-1284-1670)
- Michael C. Prabhu
- Matthias Holdhoff (ORCID: https://orcid.org/0000-0002-3285-3484)
- Chetna Wathoo
- Cameron Brennan (ORCID: https://orcid.org/0000-0003-4064-8891)
- Qun Cao
- Genaro R. Villa (ORCID: https://orcid.org/0000-0001-9461-2291)
- Zaki Abou-Mrad (ORCID: https://orcid.org/0000-0001-6387-8396)
- Brian J. Coyne (ORCID: https://orcid.org/0000-0001-9305-6473)
- Wen Jiang (ORCID: https://orcid.org/0000-0001-9154-633X)
- Isaac H. Solomon (ORCID: https://orcid.org/0000-0003-3432-0902)
- Douglas Nielsen
- Alexandra Giantini-Larsen (ORCID: https://orcid.org/0000-0002-9545-8502)
- Rachel Estrera (ORCID: https://orcid.org/0009-0006-0772-3641)
- Isaiah Osei-Gyening
- Yulong Chen (ORCID: https://orcid.org/0009-0003-1436-9300)
- Thomas P. Quinn (ORCID: https://orcid.org/0000-0003-0286-6329)
- Zhong He (ORCID: https://orcid.org/0000-0002-7369-9989)
- Jingjing Sun (ORCID: https://orcid.org/0000-0002-3087-8258)
- Md Amin Hossain (ORCID: https://orcid.org/0000-0001-7136-503X)
- Charles Couturier (ORCID: https://orcid.org/0000-0001-8015-7160)
- Jiyong Liang
- A. Chiocca
- Jordina Rincon Torroella
- Haley E. Sax
- Marla J. Polk
- Odysseas Nikas
Institutions
- Broad Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Johns Hopkins Bayview Medical Center (US)
- Center for Neuro-Oncology (US)
- Dana-Farber Cancer Institute (US)
- Center for Cancer Research (US)
- Center for Pain and the Brain (US)
- Celldex Therapeutics (United States) (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- McGill University (CA)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1126/scitranslmed.adv2881
- Citations
- 8
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 13.00