ONCOLYTIC VIRUS THERAPY
TURNING VIRUSES AGAINST CANCER

Oncolytic virus therapy uses viruses, natural or engineered, that selectively infect, replicate within, and kill cancer cells while sparing normal cells. Unlike fixed-dose chemotherapy, an oncolytic virus is a self-amplifying treatment: it multiplies inside cancer cells, producing thousands of new viral particles that infect neighboring tumor cells.

“A live, self-amplifying treatment that multiplies inside tumors, unlike any drug in oncology.”

• Why Cancer Cells Are Vulnerable

  Cancer cells disable their own antiviral defences (interferon signalling, p53, RAS/MAPK pathways) to evade the immune system. These same defects make cancer cells uniquely susceptible to viral infection — the very vulnerabilities that protect cancer become its weakness.

• T-VEC: The Approved Standard

  Talimogene laherparepvec (T-VEC/Imlygic) is an engineered HSV-1 with ICP34.5 and ICP47 deleted, approved by FDA (Oct 2015) and EMA (Dec 2015) for unresectable cutaneous, subcutaneous, and nodal melanoma lesions after initial surgery.

• From Accidental Observation to Deliberate Therapy

  Clinical observations dating to the 19th century noted cancer remissions following viral infections. Modern molecular biology enabled precise viral engineering — transforming an accidental observation into a controlled, targeted therapy.

• Converting Cold Tumours to Hot

  Many tumours are immunologically "cold" — they don't respond to checkpoint inhibitors because they lack inflammatory signals to attract T-cells. Oncolytic viruses generate intense local inflammation, converting cold tumours to hot ones responsive to immunotherapy.

The step-by-step process from viral delivery to systemic immune activation.

1. 1

   Delivery to Tumour

   Directly injected into accessible tumours (melanoma, head/neck lesions) or delivered intravenously for disseminated disease — an active area of research for systemic virotherapy.

2. 2

   Cancer Cell Recognition

   Each viral platform uses different cancer cell surface receptors: HSV targets HVEM/nectin-1; adenoviruses target CAR; Newcastle disease virus targets sialic acid residues. Viral entry is preferential for cancer cells with disrupted antiviral pathways.

3. 3

   Replication and Amplification

   Inside the cancer cell, the virus hijacks the replication machinery and produces thousands of copies. Normal cells would detect and destroy the virus via interferon; cancer cells cannot — enabling unrestricted viral replication.

4. 4

   Cancer Cell Death

   The infected cell dies via direct lytic destruction (cell bursts), apoptosis, necroptosis, and immunogenic cell death — releasing tumour antigens and danger signals that activate dendritic cells and T-cells.

5. 5

   Systemic Immune Activation

   Released tumour antigens, cytokines, and viral pathogen signals activate a systemic anti-tumour immune response — potentially attacking distant metastatic sites (the abscopal effect) beyond the injection site.

Multiple viral platforms are in clinical development, each with unique biological properties and cancer type targets.

While melanoma is the only approved indication, active clinical development spans multiple solid tumour types with accessible lesions or intratumoral delivery options.

• Melanoma (Approved)

  T-VEC is approved for unresectable cutaneous, subcutaneous, and nodal melanoma. Combination with pembrolizumab is the most studied clinical application — synergistic abscopal responses observed.

• Glioblastoma (GBM)

  G47delta approved in Japan (2021) for GBM. PVSRIPO (poliovirus, intracranial) has Breakthrough Therapy status. DNX-2401 (adenovirus) and HSV-based agents in active Phase I/II trials.

• Head and Neck Cancer

  Multiple oncolytic virus trials for squamous cell carcinoma of the head and neck, leveraging direct injection into accessible tumours and combination with anti-PD-1 checkpoint inhibition.

• Bladder Cancer (Non-Muscle Invasive)

  CG0070 (adenovirus) instilled intravesically for BCG-unresponsive NMIBC. Addresses a major unmet need for bladder preservation without cystectomy.

• Hepatocellular Carcinoma

  JX-594 (Pexa-Vec vaccinia) delivered intratumorally or intravenously for HCC. Intrahepatic injection combines direct viral oncolysis with systemic immune activation.

• Solid Tumours (Next-Gen)

  Armed oncolytic viruses carrying checkpoint inhibitors, bispecific T-cell engagers, or cytokines directly into the tumour microenvironment represent the next frontier — multiple Phase I/II trials open globally.

• 2015Year T-VEC received FDA and EMA approvalFirst oncolytic virus approved in the Western world — proof of concept for the entire class.
• 26%Durable response rate with T-VEC in OPTiM trialvs 6% for GM-CSF control — across all lesions including uninjected and visceral disease.
• 2021Year G47delta approved in Japan for GBMThe first oncolytic virus approved specifically for brain tumours — a landmark in neuro-oncology.
• 10+Oncolytic virus platforms in active clinical developmentFrom HSV to poliovirus to coxsackievirus — a broad and rapidly expanding pipeline.
• 23.3Median overall survival with T-VEC in the OPTiM trialT-VEC showed a median overall survival of 23.3 months versus 18.9 months with GM-CSF, adding an important survival benchmark alongside durable response rate.
• 84.2%1-year survival rate with G47Δ in recurrent glioblastomaIn the Japanese phase 2 study that supported approval, G47Δ achieved a 1-year survival rate of 84.2%, making it one of the most striking headline numbers in oncolytic virus therapy for brain tumors.

The two approaches are increasingly used together, but understanding their differences clarifies why the combination is so promising.

Oncolytic virus therapy has a fundamentally different and generally more favourable safety profile compared to systemic chemotherapy or high-dose immunotherapy. Most side effects are local and self-limiting.

• Flu-Like Symptoms

  The most common systemic effects are fatigue, fever, chills, and myalgia — reflecting the immune activation response. Typically mild to moderate, peak in the first 24–48 hours post-injection, and resolve spontaneously. Managed with paracetamol/NSAIDs.

• Local Injection Site Reactions

  Pain, erythema, swelling, and ulceration at the injection site are expected and indicate active viral replication. Injected lesions often form crusts and heal over weeks. Wound care and viral shedding precautions (covering the site, avoiding immunocompromised contacts) are required.

• Viral Shedding Precautions

  T-VEC contains a replicating herpes virus. Patients must avoid direct contact between treated areas and immunocompromised individuals, pregnant women, or neonates for the duration of treatment. Antiviral agents (acyclovir) are available as a safety backstop if needed.

T-VEC availability, clinical trial identification, and navigation from evaluation to treatment.

1. 1

   Eligibility Assessment

   Review of cancer type, stage, lesion accessibility, immune status, and prior treatment history to determine eligibility for T-VEC or clinical trial-based oncolytic virus therapy.

2. 2

   Trial Identification

   Active search of global trial databases for enrolling oncolytic virus trials — including G47delta programs in Japan, PVSRIPO in GBM, CG0070 in bladder cancer, and armed oncolytic virus combination trials.

3. 3

   Specialist Consultation

   Facilitation of remote consultation with an oncolytic virus specialist or clinical trial team before travel — with translated medical records transmitted in advance.

4. 4

   Travel and Logistics

   Medical visa, accommodation, and in-country support for patients accessing oncolytic virus therapy at international specialist centres, including Japan and China.

5. 5

   Post-Treatment Follow-Up

   Translation of treatment records, coordination of home oncologist handover, and support for the ongoing monitoring period including response assessment interpretation.

Each page covers one oncolytic virus topic in depth.

Frequently Asked Questions