Clinical trial links oncolytic immunoactivation to survival in glioblastoma

Alexander L. Ling, Isaac H. Solomon, Ana Montalvo Landivar, Hiroshi Nakashima, Jared K. Woods, Andres Santos, Nafisa Masud, Geoffrey Fell, Xiaokui Mo, Ayse S. Yilmaz, James Grant, Abigail Zhang, Joshua D. Bernstock, Erickson Torio, Hirotaka Ito, Junfeng Liu, Naoyuki Shono, Michal O. Nowicki, Daniel Triggs, Patrick HalloranRaziye Piranlioglu, Himanshu Soni, Brittany Stopa, Wenya Linda Bi, Pierpaolo Peruzzi, Ethan Chen, Seth W. Malinowski, Michael C. Prabhu, Yu Zeng, Anne Carlisle, Scott J. Rodig, Patrick Y. Wen, Eudocia Quant Lee, Lakshmi Nayak, Ugonma Chukwueke, L. Nicolas Gonzalez Castro, Sydney D. Dumont, Tracy Batchelor, Kara Kittelberger, Ekaterina Tikhonova, Natalia Miheecheva, Dmitry Tabakov, Nara Shin, Alisa Gorbacheva, Artemy Shumskiy, Felix Frenkel, Estuardo Aguilar-Cordova, Laura K. Aguilar, David Krisky, James Wechuck, Andrea Manzanera, Chris Matheny, Paul P. Tak, Francesca Barone, Daniel Kovarsky, Itay Tirosh, Mario L. Suvà, Kai W. Wucherpfennig, Keith Ligon, David A. Reardon, E. Antonio Chiocca

Research output: Contribution to journalArticlepeer-review


Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM) 1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110—an oncolytic herpes virus (oHSV) 3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue 4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy ( NCT03152318 ).

Original languageEnglish
Pages (from-to)157-166
Number of pages10
Issue number7985
StatePublished - 2 Nov 2023

All Science Journal Classification (ASJC) codes

  • General


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