Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses

Alexander L Ling¹, Jennifer Gantchev², Michael C Prabhu^{3

4}, Sreyashi Basu⁵, Ryuhjin Ahn⁶, Alicia D'Souza⁶, Nafisa Masud¹, Anna Ball¹, Odysseas Nikas¹, Genaro R Villa¹, Michael S Regan², Gerard Baquer², Georges Ayoub^{3

4}, Charles A Whittaker⁶, Zaki Abou-Mrad⁷, Andres Santos^{1

3}, Charles P Couturier^{2

6

8

9}, Dina Elharouni^{3

4}, Jayne Vogelzang^{3

4}, Kenny K H Yu⁷, Hong Chen⁵, Zhong He⁵, Wen Jiang¹⁰, Calixto Hope Lucas¹¹, Haley E Sax¹², Frederick F Lang¹³, Vinay K Puduvalli¹⁴, Viviane Tabar⁷, Cameron W Brennan⁷, Adrienne Boire¹⁵, Matthias Holdhoff¹⁶, Chetan Bettegowda¹⁷, Michael Cima⁶, Isaac H Solomon^{3

4}, Ying Yuan¹⁸, Paul P Tak¹⁹; Accelerating GBM Therapies TeamLab²⁰; Padmanee Sharma^{5

21}, Forest M White⁶, Keith L Ligon^{3

4}, Nathalie Y R Agar², David A Reardon²², Giacomo Oliveira^{8

12}, E Antonio Chiocca¹

Collaborators, Affiliations

Collaborators

Accelerating GBM Therapies TeamLab:
Jennifer Wiley, Kathryn Partridge, Rameen Beroukhim, Amanda Spearman, Ugonma N Chukwueke, Patrick Y Wen, Austin L H 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 W Malinowski, Sonam Bhatia, Thomas Quinn, Marla J Polk, Alexsandra B Espejo, Jingjing Sun, Yulong Chen, Sonali Jindal, Jason T Huse, Lisa Norberg, Sangeeta Goswami, Betty Y Kim, Kadir C Akdemir, Brittany Parker Kerrigan, Douglas Nielsen, Jian Hu, Pratibha Sharma, Chetna Wathoo, Gregory Buchold, Jiyong Liang, Stuart Levine, Qun Cao, Alexei Stortchevoi, Shahiba Ogilvie, Alexandra Giantini Larsen, Kelsey Hopland, Yuval Elhanati, Rachel Estrera, Isaiah Osei-Gyening, Tejus A Bale, Christopher Douville, Jordina Rincon Torroella, Vasilena Gocheva, Francesca Barone, Jennifer Moliterno

Affiliations

¹ Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
² Surgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
³ Department of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
⁵ James P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
⁶ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁸ Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁹ Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3AOG4, Canada.
¹⁰ Department of Radiation Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹¹ Department of Pathology, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹² Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
¹³ Department of Neurosurgery, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁴ Department of Neuro-Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁵ Department of Neurology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹⁶ Division of Neuro-Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹⁷ Department of Neurosurgery, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹⁸ Department of Biostatistics, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁹ Candel Therapeutics Inc., Needham, MA 02494, USA.
²⁰ Accelerating GBM Therapies TeamLab, Cambridge, MA 02142, USA.
²¹ Department of Immunology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
²² Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.

PMID: 41061048
DOI: 10.1126/scitranslmed.adv2881

Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses

Alexander L Ling et al. Sci Transl Med. 2025.

. 2025 Oct 8;17(819):eadv2881.

doi: 10.1126/scitranslmed.adv2881. Epub 2025 Oct 8.

Authors

Collaborators

Accelerating GBM Therapies TeamLab:
Jennifer Wiley, Kathryn Partridge, Rameen Beroukhim, Amanda Spearman, Ugonma N Chukwueke, Patrick Y Wen, Austin L H 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 W Malinowski, Sonam Bhatia, Thomas Quinn, Marla J Polk, Alexsandra B Espejo, Jingjing Sun, Yulong Chen, Sonali Jindal, Jason T Huse, Lisa Norberg, Sangeeta Goswami, Betty Y Kim, Kadir C Akdemir, Brittany Parker Kerrigan, Douglas Nielsen, Jian Hu, Pratibha Sharma, Chetna Wathoo, Gregory Buchold, Jiyong Liang, Stuart Levine, Qun Cao, Alexei Stortchevoi, Shahiba Ogilvie, Alexandra Giantini Larsen, Kelsey Hopland, Yuval Elhanati, Rachel Estrera, Isaiah Osei-Gyening, Tejus A Bale, Christopher Douville, Jordina Rincon Torroella, Vasilena Gocheva, Francesca Barone, Jennifer Moliterno

Affiliations

¹ Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
² Surgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
³ Department of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
⁵ James P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
⁶ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁸ Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁹ Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3AOG4, Canada.
¹⁰ Department of Radiation Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹¹ Department of Pathology, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹² Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
¹³ Department of Neurosurgery, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁴ Department of Neuro-Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁵ Department of Neurology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹⁶ Division of Neuro-Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹⁷ Department of Neurosurgery, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
¹⁸ Department of Biostatistics, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
¹⁹ Candel Therapeutics Inc., Needham, MA 02494, USA.
²⁰ Accelerating GBM Therapies TeamLab, Cambridge, MA 02142, USA.
²¹ Department of Immunology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
²² Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.

PMID: 41061048
DOI: 10.1126/scitranslmed.adv2881

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.

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Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses

Collaborators

Affiliations

Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses

Authors

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Affiliations

Abstract

MeSH terms

LinkOut - more resources

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Medical

Research Materials