Illustration of oncolytic viruses targeting cancer cells in a clinical settingIntroduction

Oncolytic viruses (OVs) represent a class of viruses that specifically target and destroy cancer cells while leaving normal healthy cells unharmed. These viruses can be either genetically modified or naturally occurring, designed to take advantage of the distinct weaknesses found in cancer cells. Upon entering the cancer cells, OVs replicate and induce cell lysis, causing the cells to burst and release new viral particles that can then infect adjacent cancer cells. Furthermore, the lysis process releases tumor antigens, which can activate the body’s immune system to identify and attack any remaining cancer cells. This dual mechanism—directly killing cancer cells and stimulating an immune response—positions oncolytic viruses as a promising strategy in cancer treatment. This news article spotlights the groundbreaking oncolytic virus-based methods recently unveiled at the 2024 American Society of Gene & Cell Therapy (ASGCT) meeting.

Overcoming Resistance and Enhancing Radiotherapy

Unraveling Resistance Mechanisms

Yale University’s groundbreaking study identified a mutation in the SH2B3 gene that leads to resistance against talimogene laherparepvec (TVEC), an FDA-approved oncolytic virus. This mutation enhances interferon signaling, creating an antiviral state within the tumor microenvironment, thereby reducing the effectiveness of OV therapies. Understanding such resistance mechanisms is crucial for improving OV efficacy. Read more

Synergy with Radiotherapy

The University of Alabama at Birmingham explored combining a genetically engineered oncolytic herpes simplex virus (oHSV) M002 with radiotherapy in treating fusion-positive rhabdomyosarcoma (FP-RMS). Their study showed that M002 significantly enhances the cytotoxic effects of radiotherapy, potentially offering a more effective treatment strategy for pediatric soft tissue sarcomas. Read more

Innovative Combination Therapies

Targeting Advanced Solid Tumors

City of Hope National Comprehensive Cancer Center investigated a novel combination of CF33-CD19, an oncolytic vaccinia virus, and blinatumomab, a bispecific T-cell engager. This combination therapy targets CD19-expressing cancer cells and has shown promising results in preclinical models, indicating enhanced anti-tumor immunity and tumor growth inhibition. Read more

Systemic Immune Activation

TILT Biotherapeutics has developed TILT-123, an oncolytic adenovirus armed with TNFa and IL-2, designed to activate and attract T cells into tumors. Systemic administration of TILT-123 resulted in significant tumor transduction and lymphocyte accumulation, highlighting its potential as an effective intravenous therapy for immunologically cold tumors. Read more

Novel Delivery Mechanisms

Virus-Activated Killer Cell Therapy

Hubei Cancer Hospital’s innovative VAK cell therapy involves using UV-treated oncolytic HSV-2 to activate killer cells for treating malignant pleural and peritoneal effusions. This approach has shown significant reductions in effusion volumes and improved overall survival in stage IV lung cancer patients, showcasing its potential as a safe and effective treatment option. Read more

Systemic Virotherapy

Calidi Biotherapeutics introduced a systemic enveloped oncolytic virotherapy targeting multiple tumor sites using the vaccinia virus RT-01. The virus is engineered with an additional human cell-derived membrane to evade immune system elimination, showing effective tumor targeting and protection against immune responses. This presents a promising solution for metastatic diseases. Read more

Combining Oncolytic Viruses with Traditional Therapies

Integrating Chemotherapy

Beijing Tsinghua Changgung Hospital combined the oncolytic virus H101 with hepatic arterial infusion chemotherapy (HAIC) using modified FOLFOX for treating intrahepatic mass-forming cholangiocarcinoma (IMCC). This combination therapy demonstrated significant anti-tumor effects, immune activation, and improved quality of life for patients, suggesting a viable strategy for IMCC. Read more

Monotherapy Potential

City of Hope National Comprehensive Cancer Center conducted a phase 1 study of CF33-hNIS, an oncolytic vaccinia virus engineered with the human sodium-iodide symporter (hNIS) gene for gastrointestinal malignancies. The therapy showed selective replication in tumor cells and significant anti-tumor immunity, particularly in cholangiocarcinoma patients, supporting further investigation as both monotherapy and in combination with immune checkpoint inhibitors. Read more

Advancements in Glioblastoma and Glioma Therapies

Glioblastoma Treatments

Sanbo Brain Hospital and Queen Mary University of London evaluated Ad-TD-nsIL12, an oncolytic adenovirus, in patients with recurrent glioblastoma (rGBM). This therapy demonstrated safety and effectiveness with enhanced T cell infiltration in treated tumors, warranting further phase II clinical studies. Read more

Neural Stem Cell-Based Virotherapy

City of Hope National Medical Center explored a neural stem cell-based oncolytic virotherapy for recurrent high-grade gliomas. This innovative approach uses neural stem cells to protect and deliver oncolytic viruses, showing promising safety and potential efficacy with ongoing enrollment to determine the maximum tolerated dose. Read more

Exploring Immune-Refractory and Advanced Tumors

Targeted Adenovirus for HER2-Positive Tumors

Baylor College of Medicine is exploring a binary oncolytic adenovirus in combination with HER2-specific CAR T cells for treating HER2-positive solid tumors. Early results from this phase I clinical trial indicate promising anti-tumor activity with a focus on evaluating the safety and maximum tolerated dose. Read more

Enhancing Immune Responses

The University of Texas MD Anderson Cancer Center’s phase 2 trial is investigating AdAPT-001, an oncolytic adenovirus with a TGF-β trap combined with immune checkpoint inhibitors for treating immune-refractory cancers. This combination therapy aims to enhance immune responses and improve clinical outcomes in resistant cancer types. Read more

Combining IL-12 and PD-1 Antibody

MD Anderson Cancer Center’s phase 1 trial of T3011, an oncolytic HSV expressing IL-12 and anti-PD-1 antibody, showed safety and preliminary efficacy in advanced solid tumors and malignant pleural effusion or ascites. This dual approach suggests a promising therapeutic strategy. Read more

Pioneering New Horizons

Oncolytic Virus for Esophageal Cancer

Memorial Sloan Kettering Cancer Center’s phase 1 study investigated the safety of endoscopically injected OBP-301, an oncolytic adenovirus, in medically inoperable esophageal cancer. The study found no dose-limiting toxicities, supporting further evaluation in larger cohorts. Read more

Hepatocellular Carcinoma Innovations

The University of Maryland School of Medicine is evaluating RP2, an oncolytic HSV with GM-CSF and anti-CTLA-4, in combination with atezolizumab and bevacizumab for advanced hepatocellular carcinoma. This combination aims to enhance immune responses and improve treatment efficacy. Read more

Real-World Biosimilar Evaluation

CVS Health conducted a real-world evaluation of oncology biosimilars, comparing treatment adherence and out-of-pocket costs to reference branded products. The study found that biosimilars provided significant cost savings and high adherence rates, supporting their broader adoption in clinical practice. Read more

High-Grade Gliomas

A collaborative study by City of Hope and multiple institutions is evaluating neural stem cell-based oncolytic virotherapy for high-grade gliomas. Early results indicate safety and potential efficacy with ongoing enrollment to determine the maximum tolerated dose. Read more

Expanding Therapeutic Potential

Pediatric Sarcomas

The University of Alabama at Birmingham assessed the efficacy of combining oncolytic viruses with chemoradiotherapy for pediatric sarcomas. The study found enhanced responses, suggesting that oncolytic virotherapy can serve as a valuable adjunct to traditional treatments in pediatric oncology. Read more

Novel Treatment Paradigms

Washington University School of Medicine is investigating a combination of long-acting IL-7 and oncolytic Zika virus for glioblastoma. This approach significantly improved T cell infiltration and survival in preclinical models, offering a new treatment paradigm for this aggressive cancer. Read more

Ovarian Cancer

TILT Biotherapeutics and Mayo Clinic’s phase 1 trial combined an oncolytic adenovirus with pembrolizumab for platinum-resistant ovarian cancer. The combination showed safety and disease control, highlighting the potential for oncolytic viruses to enhance checkpoint inhibitor efficacy. Read more

Melanoma with Liver Metastasis

Peking University Cancer Hospital evaluated a combination of an anti-PD-1 antibody, axitinib, and an oncolytic virus for mucosal melanoma with liver metastasis. The phase 1 trial showed preliminary efficacy and manageable toxicity, indicating potential for treating liver metastases in melanoma. Read more

Oncolytic Virus for Solid Tumors

City of Hope National Comprehensive Cancer Center’s phase 1 trial of CF33-hNIS for gastrointestinal malignancies showed significant anti-tumor activity, with plans for further studies to assess combination therapies and expand indications. Read more

Recurrent Glioblastoma

Sanbo Brain Hospital and collaborators are investigating a novel oncolytic adenovirus for recurrent glioblastoma. The phase 1 study demonstrated safety and clinical benefit, suggesting further exploration in phase II trials. Read more

Advanced Solid Tumors

Boehringer Ingelheim’s phase 1 trial of BI 1821736, an oncolytic virus for advanced solid tumors, showed a manageable safety profile and potential anti-tumor activity, supporting continued development. Read more

Conclusion

Oncolytic virotherapy is poised to revolutionize cancer treatment, offering targeted immune-stimulating options that enhance existing therapies and provide new hope for patients with resistant or advanced cancers. The future of cancer treatment looks promising as researchers continue to explore and refine these innovative strategies.

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Illustration of oncolytic viruses targeting cancer cells in a clinical setting