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3ms
A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov)
P1, N=62, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Immunomodulating
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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cyclophosphamide • CAN-3110
5ms
Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy. (PubMed, Neuro Oncol)
This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.
Journal • Oncolytic virus • IO biomarker
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CD8 (cluster of differentiation 8) • IGF2 (Insulin-like growth factor 2)
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CAN-3110
9ms
BostonGene Announces Publication in Nature (Businesswire)
P1 | N=62 | NCT03152318 | "BostonGene...today announced the online publication...in Nature...Utilization of immunotherapy for GBM has been challenging due to the scarcity of infiltrating antitumor lymphocytes caused by a highly immunosuppressive or 'lymphocyte-depleted' tumor microenvironment (TME)....The results demonstrated a single injection of CAN-3110 activated an antitumor immune response in GBM, inducing defined changes in T cell repertoires and tumor transcriptomic signatures. These findings are evidence that intralesional onolytic viruses can convert the immunosuppressive GBM TME to an immunoactivated state that is more responsive to immunotherapy."
P1 data
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CAN-3110
1year
Oncolytic immunotherapy links immunoactivation to subject survival in phase I trial of recurrent glioblastoma (SNO 2023)
Combined with a lack of observed dose-limiting toxicities and a median post-treatment survival of 14.2 months (95% CI: 9.5-15.7) in IDHwt rGBM patients with positive HSV1 serology, these data provide evidence that intralesional CAN-3110 treatment can instigate immune activation in a traditionally immunologically cold tumor and that this immune activation may influence survival time—particularly when patients have had prior exposure to HSV1. (clinicaltrials.gov NCT03152318)
Clinical • P1 data • Oncolytic virus • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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IDH wild-type
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CAN-3110
1year
Clinical trial links oncolytic immunoactivation to survival in glioblastoma. (PubMed, Nature)
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)...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 (ClinicalTrials.gov: NCT03152318 ).
Journal • Oncolytic virus
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NES (Nestin)
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CAN-3110
almost2years
A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov)
P1, N=62, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2024
Trial completion date • Trial primary completion date • Immunomodulating
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation • IDH1 R132H • IDH wild-type • IDH1 R132
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cyclophosphamide • CAN-3110
2years
A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov)
P1, N=62, Recruiting, Dana-Farber Cancer Institute | Active, not recruiting --> Recruiting
Enrollment open • Immunomodulating
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation • IDH1 R132H • IDH wild-type • IDH1 R132
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cyclophosphamide • CAN-3110
2years
ONCOLYTIC HERPES SIMPLEX VIRUS IMMUNO-VIROTHERAPY IN COMBINATION WITH TIGIT IMMUNE CHECKPOINT BLOCKADE TO TREAT GLIOBLASTOMA (SITC 2022)
Conclusions Our findings show that the combination of HSV-1 rQNestin34.5v2 virotherapy with anti-TIGIT checkpoint blockade immunotherapy represents a promising strategy to overcome primary resistance to immune checkpoint inhibitors in GBM. Ethics Approval All animal experiments and procedures described in this study were approved by Brigham and Women's Institutional Animal Care and Use Committee.
Combination therapy • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD8 (cluster of differentiation 8) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • PVR (PVR Cell Adhesion Molecule) • NES (Nestin) • CX3CR1 (C-X3-C Motif Chemokine Receptor 1) • NECTIN2 (Nectin Cell Adhesion Molecule 2)
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IDH1 mutation • IDH wild-type
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CAN-3110
over2years
Oncolytic HSV-1 rQNestin34.5v2 Sensitizes IDH1-mutated Glioma to Immunotherapy (ASGCT 2022)
These datademonstrate that mouse gliomas expressing IDH1 resemble human glioma cellsharboring IDH1 and are suitable models to study translational immunotherapiesfor low grade gliomas. Experiments to address the therapeutic andimmunostimulatory potential of intratumoral HSV-1 administration in primary andrecurrent IDH1-mutant gliomas are ongoing.
PD(L)-1 Biomarker • IO biomarker
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TERT (Telomerase Reverse Transcriptase) • LAG3 (Lymphocyte Activating 3) • ATRX (ATRX Chromatin Remodeler) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PVR (PVR Cell Adhesion Molecule) • NES (Nestin)
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TP53 mutation • IDH1 mutation • TERT mutation • IDH wild-type • TERT promoter mutation
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CAN-3110
over2years
NOTCH induced MDSC recruitment after oHSV virotherapy in CNS cancer models modulates anti-tumor immunotherapy. (PubMed, Clin Cancer Res)
NOTCH induced immunosuppressive myeloid cell recruitment limited anti-tumor immunity. Translationally, these findings support the use of NOTCH inhibition in conjunction with oHSV therapy.
Preclinical • Journal • IO biomarker
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CD8 (cluster of differentiation 8) • IL10 (Interleukin 10) • CCL2 (Chemokine (C-C motif) ligand 2) • JAG1 (Jagged Canonical Notch Ligand 1)
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JAG1 expression
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CAN-3110
3years
Modulation of the IL-27 receptor signaling pathway in glioblastoma and oncolytic virotherapy (SNO 2021)
Despite positive functional modifications on CD4 + T cells, global lack of IL-27R signaling promoted tumor growth accompanied by increased circulating myeloid derived suppressor cells (MDSCs) in the GL261 model. Experiments to address the immunoregulatory role of IL-27R signaling during HSV-1 rQNestin34.5v2 virotherapy-induced glioma tissue destruction are ongoing.
Oncolytic virus • PD(L)-1 Biomarker • IO biomarker
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HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule) • IL10 (Interleukin 10)
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CAN-3110
3years
Treatment of glioblastoma with current oHSV variants reveals differences in efficacy and immune cell recruitment. (PubMed, Mol Ther Oncolytics)
Furthermore, the CT2A model was completely resistant to virus therapy, while in the GL261N4 model rQNestin34.5v1 treatment resulted in enhanced macrophage recruitment, impaired tumor progression, and long-term survival of a few animals. We conclude that prolonged intratumoral viral presence correlates with immune cell recruitment, and both are needed to enhance anti-tumor immunity.
Clinical • Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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CAN-3110