Mechanism

T-VEC is an attenuated HSV-1 with two viral genes deleted and two transgenes inserted:

ICP34.5 deletion — restricts replication to tumour cells, which lack the antiviral pathways that prevent HSV growth in normal cells.
ICP47 deletion — improves antigen presentation by the infected tumour cell.
GM-CSF transgene — secreted locally, recruits antigen-presenting cells, primes a systemic T-cell response.

The result is direct oncolysis of injected lesions plus a measurable, though usually modest, abscopal response in non-injected lesions.

Indications (UK)

NICE TA Unresectable stage IIIB, IIIC or IVM1a melanoma — cutaneous, subcutaneous or nodal metastases that are accessible to direct injection — NICE TA410 (2016).
No bone, brain, lung or other visceral metastases.
Not used for stage IV with visceral disease — systemic immunotherapy is preferred for that population.
Combination with checkpoint inhibitors (ipilimumab, pembrolizumab): tested in trials (MASTERKEY-265) with promising response rates; not standard NHS practice and discussion at melanoma MDT required.

Dosing and administration

Vial concentrations

Initial dose: 10⁶ PFU/mL (low-titre).
Subsequent doses: 10⁸ PFU/mL (high-titre).

Schedule

Dose 1: up to 4 mL at 10⁶ PFU/mL.
Dose 2: 3 weeks later — up to 4 mL at 10⁸ PFU/mL.
Dose 3 and onwards: every 2 weeks at 10⁸ PFU/mL.
Continue for at least 6 months, until no injectable lesions, or until disease progression / unacceptable toxicity.

Volume per lesion (per SmPC)

Lesion > 5 cm: up to 4 mL.
2.5–5 cm: up to 2 mL.
1.5–2.5 cm: up to 1 mL.
0.5–1.5 cm: up to 0.5 mL.
≤ 0.5 cm: up to 0.1 mL.

Inject the largest, most accessible lesions preferentially. Use multiple needle tracks within a lesion to ensure even distribution. Avoid injection into mucosal sites, areas with thin overlying skin and over major neurovascular structures.

Adverse events

Injection site reactions: pain, erythema, swelling, occasional cellulitis-like inflammation.
Flu-like illness: fever, chills, fatigue, myalgia for 24–72 hours after injection — commonest with the first high-titre dose.
Nausea, headache.
Herpetic infection: rare in the patient; theoretical risk to immunosuppressed contacts and healthcare workers.
Vitiligo / depigmentation around injected lesions occasionally.
Discontinuation rates in OPTiM were low.

Biosafety & infection control

T-VEC is a live attenuated virus. Standard precautions plus contact and droplet precautions are recommended during administration.
Healthcare workers who are immunosuppressed or pregnant should not handle or administer T-VEC.
Caregivers and close contacts at risk: pregnant women, immunosuppressed individuals, neonates and patients with active herpetic lesions. Counsel patient and household.
Cover injection sites with an occlusive dressing for the first week; advise on safe disposal of contaminated dressings (clinical waste).
If the patient develops a suspected herpetic lesion at the injection site or elsewhere, acyclovir is effective.
Avoid HSV-naive caregivers (e.g. children) handling fresh wound dressings.

Evidence summary

Trial OPTiM (Andtbacka 2015, J Clin Oncol): phase 3 RCT of T-VEC vs subcutaneous GM-CSF in 436 patients with unresectable stage IIIB–IV melanoma. Durable response rate (continuous response ≥ 6 months) 16.3% vs 2.1%; overall response rate 26.4% vs 5.7%; complete response rate 10.8% vs 0.7%. OS benefit predominantly in stage IIIB / IIIC / IVM1a subgroup.
Trial MASTERKEY-265 phase 1b (Ribas 2017): T-VEC + pembrolizumab in advanced melanoma — ORR ~62% with manageable safety. Subsequent phase 3 did not meet primary endpoint — combination remains investigational.
Stage IIIB–IVM1a remains the population where benefit is most clearly demonstrated.

Practical considerations

Local melanoma MDT decision; provided in specialist centres with intralesional therapy experience.
Image-document each lesion at baseline; track response by RECIST or modified response criteria for intralesional therapy (irRC / iRECIST-like).
Cold-chain storage required (frozen at −90 to −70°C); thawing protocol per SmPC.
Patient counselling: live virus, contact precautions, biosafety, expected flu-like reaction after the first high-titre dose.
Surgical excision of remaining lesions after T-VEC response is reasonable in selected cases (‘immunological neoadjuvant’ approach).
Pre-treatment HSV serology is not routinely required; HSV-seropositive patients respond as well as seronegative.

T-VEC — talimogene laherparepvec