linoserpaturev (CAN-3110) / Candel Therap - LARVOL DELTA

Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma. (PubMed, Oncogene) - P1 | "Matched tumor biopsies pre- and post-oHSV (CAN-3110, NCT03152318) treatment revealed an induction of DLL4 post-therapy...Co-culture of infected tumor cells with immune cells revealed that OVsDLL4 treatment polarized them toward an inflammatory phenotype. In vivo, the therapeutic efficacy of OVsDLL4 was underscored, as treatment of glioma-bearing mice resulted in reduced tumor burden and prolonged survival."

Journal • Preclinical • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor • DLL4

EVOV-induced immune pressure reshapes glioblastoma cell states and spatial immune visibility (EANO 2026) - "EVOV-induced pathways were converted into ssGSEA signatures and assessed in tumors from patients treated with oHSV-1 (CAN-3110). EVOV reshaped PBMCs toward a cytotoxic state, expanding CD8 T, NKT, and NK cells while reducing Tregs, and enhancing GSC killing... EVOV-driven immune and antigen-presentation programs align with clinical response signatures, linking models to patient outcomes. Vesicle-mediated signals from oHSV-conditioned GSCs drive immune activation, tumor remodeling, reduced stemness, and increased immune visibility, defining a virus-free immunotherapy platform while exposing persistent spatial escape mechanisms."

IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD8 • IFNG • NLRC5 • PD-1 • TAP1

The Company expects to present potential long-term survival data from arm C of its phase 1b clinical trial of linoserpaturev in patients with recurrent high-grade glioma (rHGG) in Q4 2026. (The Manila Times)

Trial status • High Grade Glioma

IDH1-R132H enhances oncolytic HSV-1 therapy by facilitating viral entry and immune activation in glioma. (PubMed, Nat Commun) - "However, elevated expression of poliovirus receptor (PVR) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating leukocytes suggests a potential resistance mechanism to virotherapy. Combining rQNestin34.5 v.2 with TIGIT blockade enhances therapeutic efficacy compared to monotherapy, identifying IDH1-R132H as a potential predictive biomarker for oncolytic virotherapy response."

IO biomarker • Journal • Astrocytoma • Brain Cancer • Glioma • Herpes Simplex • Infectious Disease • Oncology • Solid Tumor • IDH1 • IFNG • NECTIN1 • TIGIT

Anticipated Milestones:…Linoserpaturev (CAN-3110) (GlobeNewswire) - "The Company expects to present mature mOS data and an update on long-term survivors from arm C of its phase 1b clinical trial of linoserpaturev in patients with rHGG in Q4 2026."

P1 data • High Grade Glioma

Blockade of cell-ECM interaction with an oncolytic virus suppresses tumoral STING activation while inducing antitumor immunity (AACR 2026) - P1 | "To investigate ways to improve its therapeutic index, we analyzed the transcriptomic changes in patients with recurrent brain tumor pre and post CAN-3110 treatment (NCT03152318)...To our knowledge, this is the first report to describe an oHSV that can inhibit innate intracellular anti-viral immunity in tumor cells and can also stimulate innate immune responses in the TME to guide antitumor immunity. Collectively, this study uncovers the significance of OV-x44 as a potent immune stimulating anticancer therapeutic."

Oncolytic virus • Brain Cancer • Melanoma • Oncology • Solid Tumor • SPP1 • STING • TLR7

Pre-existing T cells drive durable anti-tumor immunity after oncolytic virus therapy in glioblastoma (AACR 2026) - P1 | "We recently reported that survival correlated with immune activation signatures in rGBM patients receiving the oncolytic HSV-1 (oHSV) rQNestin34.5v.2 (CAN-3110)... These results provide in-situ evidence that a single intratumoral oncolytic virus injection can amplify pre-existing T cells clones and induce sustained T cell mediated tumor cytotoxicity even after virus clearance. This suggests that oncolytic virotherapy is as potent T cell activating strategy in rGBM."

Oncolytic virus • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • CD69 • CD8 • GZMB • ITGAE • NR4A1

Dissecting oncolytic virus anti-virus vs anti-tumor immunity in glioma: Insights from a patient derived organoid model (AACR 2026) - "Intratumoral injection of the oncolytic herpes simplex virus (oHSV) CAN-3110 remodels the immunosuppressive microenvironment of recurrent glioblastoma...Immune-mediated tumor cell killing was detected, both with and without virus treatment in PBMC x pGBO co-culture, using imaging and molecular readouts. This model enables investigation of how oncolytic HSV infection modulates immune response and provides a tractable system to dissect anti-tumor vs. anti-virus immune responses."

Clinical • IO biomarker • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CASP3 • CD20 • CD4 • CD8 • GZMB

IDH1-R132H enhances oncolytic HSV-1 therapy by facilitating viral entry and immune activation in glioma (AACR 2026) - "Combining rQNestin34.5v.2 with TIGIT blockade enhanced therapeutic efficacy and improved survival outcomes compared to monotherapy. Collectively, these data demonstrate that IDH1-R132H reshapes both viral entry pathways and antiviral immune defenses, identifying it as a predictive biomarker for oncolytic virotherapy response."

IO biomarker • Astrocytoma • Brain Cancer • Glioma • Oncology • Solid Tumor • IDH1 • IFNG • NECTIN1 • PVR • TIGIT

Assessing biomarker reproducibility for glioblastoma patient response stratification (AACR 2026) - "PAM clustering of MCP immune signatures, as reported for the DNX-2401 OV+Anti-PD1 trial, also stratified post-treatment survival in the CAN-3110 OV trial (p < 0.01), with the coldest TME subtype consistently predicting worse survival. While no individual immune signature is universally predictive in GBM immunotherapy, certain post-treatment cytokine signatures and TME stratifications are significant in multiple immunotherapy contexts, though not in standard-of-care patient cohorts. Marked spatiotemporal heterogeneity in these signatures underscores the need for composite prognostic markers resilient to sampling variance."

Biomarker • Clinical • IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Preclinical toxicology and efficacy of NG34C: A novel oncolytic HSV-1 expressing truncated GADD34 gene for the treatment of glioblastoma (AACR 2025) - "We recently completed a Phase I clinical trial of rQNestin34.5v2 (CAN-3110), an oncolytic virus encoding the viral neurovirulence gene ICP34.5 under the nestin promoter, demonstrating safety at doses up to 1 x 1010 PFU (Ling et al., Nature, 2023)...These results establish NG34C as a safe, hypoxia-adapted, and effective oncolytic virus for GBM. NG34C is now being produced under GMP for an upcoming INS-clinical study."

IO biomarker • Late-breaking abstract • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN2A • EGFR • NES • PPP1R15A • PTEN

Linoserpaturev (CAN-3110) - Recurrent High-Grade Glioma (rHGG) (Yahoo Finance) - "The Company submitted an IND for linoserpaturev to advance the development of this asset in rHGG in Q4 2025 and received clearance from the FDA in Q1 2026....The Company expects to present mature mOS data and an update on long-term survivors from arm C of its phase 1b clinical trial of linoserpaturev in patients with rHGG in Q4 2026."

IND • P1 data • High Grade Glioma

Persistent spatial immune responses in glioblastoma following oncolytic virus therapy. (PubMed, Cytokine Growth Factor Rev) - P1 | "A recent first-in-human clinical trial of the oncolytic herpes simplex virus rQNestin34.5 v.2 (NCT03152318) shows that a single intratumoral dose can trigger durable T-cell activation and sustained cytotoxic engagement within tumor tissue...These findings indicate that oncolytic virotherapy can remodel tumor-immune architecture and establish lasting spatial immune surveillance. This correspondence discusses the mechanistic and translational implications of persistent spatial T-cell immunity in GBM."

First-in-human • Journal • Brain Cancer • Glioblastoma • Herpes Simplex • Oncology • Solid Tumor

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2 (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Enrollment closed • Trial completion date • Trial primary completion date • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • Ependymoma • Ganglioglioma • Glioblastoma • Glioma • High Grade Glioma • Immunology • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Clinical outcomes in recurrent glioblastoma with oncolytic virotherapy: a review. (PubMed, Mol Biol Rep) - "For instance, CAN-3110, a Nestin-promoter-driven herpes simplex virus-1 (HSV-1), demonstrated a median overall survival of 14.9 months in patients with recurrent GBM, with HSV-1 seropositive patients achieving more prolonged survival (14.2 versus 7.8 months in seronegative patients). This review aims to synthesize the current evidence on clinical outcomes in patients with recurrent GBM receiving oncolytic virotherapy, with a specific focus on safety profiles, therapeutic efficacy, and survival outcomes."

Clinical data • Journal • Review • Brain Cancer • Glioblastoma • Herpes Simplex • Oncology • Solid Tumor • NES

Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial. (PubMed, Cell) - P1 | "A recent first-in-human clinical trial demonstrated that survival in glioblastoma (GBM) patients following rQNestin34.5v.2 oncolytic virus treatment was associated with immune activation signatures...Viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM."

First-in-human • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • GZMB

Candel Therapeutics to Present at the 7th Annual Glioblastoma Drug Development Summit (GlobeNewswire) - "Dr. Barone will share insights from Candel’s HSV-based platform and the linoserpaturev (CAN-3110) program in recurrent high-grade glioma (rHGG) through workshop presentations and panel discussions focused on advancing biomarker-driven clinical development in glioblastoma."

Clinical • Glioblastoma • High Grade Glioma

CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation. (PubMed, J Immunother Cancer) - "Here, we identify that immunosuppressive eADO signaling in the TME is a major barrier to oHSV therapy and CD73 blockade prevents tumor immune escape. The combination of oHSV with CD73 blockade supports the development of an antitumor immune memory response in solid tumors. This study supports clinical development of this combination strategy."

IO biomarker • Journal • Brain Cancer • Gene Therapies • Herpes Simplex • Oncology • Solid Tumor • ADORA2B • CD4 • CD73 • ENTPD1 • NT5E

Oncolytic HSV-1-Mediated JAG1 Blockade Induces Glioma Senescence-Associated Secretory Phenotype to Increase Macrophage Activation and Cetuximab-Mediated Senolysis. (PubMed, Cancer Res) - "Clinically, the Notch ligand JAG1 was upregulated in recurrent high-grade glioma patients treated with the oHSV CAN-3110 and correlated with poor prognosis. Heightened EGFR activation in senescent cells was a mechanism to escape cell death, which created a unique opportunity for cetuximab as a senolytic agent. Combination therapy reduced EGFR signaling and induced macrophage-mediated antibody-dependent cellular cytotoxicity, thereby increasing the anti-tumor therapeutic efficacy of OD-0J1."

Journal • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor • CDK1 • HMGB1 • IL1B • JAG1

Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients (SNO 2025) - "These metabolic patterns suggest that purine metabolism plays a key role in shaping immunologically active tumor microenvironments following treatment.Together, these findings provide novel mechanistic insights into the evolving tumor-immune landscape during rQnestin34.5v.2 therapy in glioblastoma, highlighting purine metabolism as a potential driver of immune activation within the tumor microenvironment. This integrated spatial approach offers a powerful framework to guide the development of more effective immunotherapeutic strategies for this challenging malignancy."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor • CD4 • OLIG2 • SOX2

Immune profiling of GBM tumor tissues collected longitudinally from patients treated with an oncolytic virus (SNO 2025) - "To evaluate safety of accessing the brain multiple times and to interrogate immune responses with an immunomodulatory agent, we are conducting a trial in which GBM patients receive intra-tumoral injections with oncolytic herpesvirus (HSV) (CAN-3110, aka rQNestin34.5v.2)...At day 90, we observed a shift in TAMs from pro-inflammatory to a more immunosuppressive phenotype with an increase in Trem2+SPP1+ TAMs and HIF1a+ hypoxic microglial cells, suggesting a compensatory inhibitory response to the initial immune response.Our studies highlight a dynamic immune response of both effector and immunosuppressive cells. These data suggest that immunotherapeutic strategies should be further developed and evaluated in the context of serial biopsies to guide our understanding of human immune responses, which may enable an iterative process to identify agents that will drive effective anti-tumor responses."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CCR7 • CD4 • CD8 • CD86 • CDK1 • CTLA4 • CXCL10 • CXCL9 • GZMK • HIF1A • IFNG • LAG3 • PD-1 • SPP1

On-Treatment Spatiotemporal Profiling of Glioblastoma During Oncolytic ImmunoTherapy (SNO 2025) - "To address this critical gap, we implemented a novel on-therapy, longitudinal, and multi-regional tissue sampling strategy in patients treated with rQNestin34.5v2, an engineered oncolytic biologic based on herpes simplex virus 1, to explore how tumor and immune ecosystems evolve during treatment.Using high-resolution spatial transcriptomics (Xenium) and targeted spatial proteomics (CyCIF), we profiled over 80 spatially and temporally distinct samples from six patients, capturing over half a million immune, stromal, and malignant cells...By the time of radiographic progression, these lymphoid structures had largely dissipated—underscoring the importance of on-treatment sampling in capturing transient, treatment-responsive immune architectures.While these findings are preliminary, they suggest a transient immune structure linked to early therapeutic response, whose collapse may contribute to treatment resistance. Our study illustrates how integrative, on-therapy spatial..."

Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor

Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients (SNO 2025) - "These metabolic patterns suggest that purine metabolism plays a key role in shaping immunologically active tumor microenvironments following treatment.Together, these findings provide novel mechanistic insights into the evolving tumor-immune landscape during rQnestin34.5v.2 therapy in glioblastoma, highlighting purine metabolism as a potential driver of immune activation within the tumor microenvironment. This integrated spatial approach offers a powerful framework to guide the development of more effective immunotherapeutic strategies for this challenging malignancy."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Herpes Simplex • Solid Tumor • CD4 • OLIG2 • SOX2

Multi-omic and single cell assessment of serial biopsies reveals responses to CAN-3110 oncolytic immunotherapy in recurrent glioblastoma that are not evident by routine clinical analyses (SNO 2025) - P1 | "These results show that longitudinal tissue sampling during rGBM clinical trials is well tolerated and, even with a small number of patients, can reveal critical mechanistic insights into a therapy's impact that would be missed via routine clinical monitoring. (clinicaltrials.gov NCT03152318)"

Biopsy • Clinical • IO biomarker • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD4

Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients (WFNOS 2025) - "These metabolic patterns suggest that purine metabolism plays a key role in shaping immunologically active tumor microenvironments following treatment.Together, these findings provide novel mechanistic insights into the evolving tumor-immune landscape during rQnestin34.5v.2 therapy in glioblastoma, highlighting purine metabolism as a potential driver of immune activation within the tumor microenvironment. This integrated spatial approach offers a powerful framework to guide the development of more effective immunotherapeutic strategies for this challenging malignancy."

Clinical • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Solid Tumor • CD4 • OLIG2 • SOX2