Melanoma is where immunotherapy injected into a tumor was first approved.

Standard care. Localized melanoma is treated with wide excision, with or without sentinel node biopsy. Stage III disease receives adjuvant nivolumab or pembrolizumab, or dabrafenib plus trametinib for BRAF V600-mutant tumors. Stage IV disease is treated with nivolumab plus relatlimab (Opdualag) first line, nivolumab plus ipilimumab, BRAF/MEK inhibitors for V600-mutant disease, and tebentafusp for uveal melanoma. Two injected treatments are approved: talimogene laherparepvec (T-VEC), an oncolytic herpes virus approved in 2015 for unresectable melanoma lesions, and, since 6 August 2026, vusolimogene oderparepvec (RP1) with nivolumab for melanoma that has progressed on anti-PD-1 therapy [1]. Lifileucel, a tumor-infiltrating lymphocyte therapy, is also approved after anti-PD-1.

What the approved injected agents do. T-VEC is a single oncolytic virus; RP1 is an oncolytic virus given with intravenous nivolumab. Their approvals cover those products, not WCI's combination.

What is done here. Image-guided ablation of an accessible melanoma deposit, by cryoablation or pulsed electric field (PEF) ablation depending on the site, followed in the same session by injection of several immune-active agents together into the ablated tumor: checkpoint inhibitors, costimulatory agonists and a TLR agonist.

Melanoma's usual sites of spread (skin, lymph nodes, lung, liver, bone) are accessible to image-guided ablation and direct injection. The rationale: progression on Opdualag or nivolumab plus ipilimumab often reflects immune suppression at the resistant site; ablation exposes tumor antigens, and the injected agents are intended to re-engage the immune response there.

This multi-agent combination is offered under physician review. In our clinical observations, treating one tumor produces a response at untreated tumors elsewhere; responses at untreated sites have been documented in some melanoma studies.

The procedure, step by step

1. Case review. Imaging; biopsy reports (BRAF, NRAS, KIT, NF1, HLA type, subtype); the full prior immunotherapy and targeted-therapy history. The Williams Cancer Institute team reads them.
2. Protocol design. The intratumoral combination is tuned to mutation profile, subtype and immune history; T-VEC is added to the combination in selected cases.
3. Guidance and ablation. Image-guided percutaneous access; PEF or cryoablation depending on the site.
4. Intratumoral injection. Through the same access, into the ablation bed, in the same session.
5. Setting and time. Most procedures are outpatient under conscious sedation; general anesthesia or an overnight stay is rarely required. About an hour for the procedure and about two hours' recovery.
6. Follow-up. Imaging at 6 to 8 weeks. Repeat procedures as indicated; the number of treatments is decided with the patient's physician. The patient's medical, surgical and radiation oncology teams are kept informed.

Agents. The injected immunotherapy is a multi-agent combination. The agents and doses are set per patient by the treating physician.

The immune conversion cycle, in clinical terms. Ablation disrupts the tumor and exposes its full antigen repertoire, not a pre-selected subset. The injected immunotherapy then remodels the tumor microenvironment, priming, recruiting and activating immune cells and releasing the brakes on them. Immune-mediated lysis exposes further antigens, which re-prime the response (epitope spreading), producing a broader, polyclonal, systemic response with memory, converting a cold tumor hot. This is WCI’s stated rationale, in Dr. Goodyear’s framing, borne out in our clinical observations.

Evidence. The pharmacological case for the intratumoral route comes from a mouse study: in mice with colorectal tumors and no ablation, anti-CTLA-4 injected into a tumor reached about 14 times the day-7 level of intravenous dosing in that tumor, the untreated tumor received no more than with intravenous dosing, and half the dose reached the blood within an hour [2]. That is mouse data in colorectal cancer; it does not test ablation and does not support a distant-site effect.

For injected immunotherapy in melanoma, the approval of RP1 with nivolumab rested on objective responses in 24.2% of 91 patients, with a median duration of response of 14.1 months [1].

WCI's record cites two intratumoral trials as supportive of the concept: the phase 3 neoadjuvant PIVOTAL trial of daromun, an immunocytokine given before surgery in resectable stage III disease, which reported a recurrence-free survival hazard ratio of 0.59 in 256 patients [3], and the phase 2 BO-112 trial (SPOTLIGHT-203). Neither daromun nor BO-112 is approved, and neither is what WCI injects.

Ablation combined with multi-agent intratumoral immunotherapy is the approach we use, in our clinical observations. No published WCI melanoma series exists. Sources

1. U.S. Food and Drug Administration, accelerated approval of vusolimogene oderparepvec (RP1, Tudriqev) with nivolumab for melanoma progressing on anti-PD-1 therapy, 6 August 2026 (objective response 24.2% in 91 patients; median duration of response 14.1 months). FDA notice
2. Meyblum L, et al. Journal for ImmunoTherapy of Cancer 2023. PMID 37949616. DOI 10.1136/jitc-2023-007433.
3. Hauschild A, Hassel JC, … Kähler KC. Neoadjuvant intralesional daromun (L19IL2/L19TNF) in resectable locally advanced melanoma: an update on the efficacy and safety results of the PIVOTAL phase III trial. Journal of Clinical Oncology 2026. DOI 10.1200/JCO-26-00852.
4. Shree T, et al. Clinical Cancer Research 2025. PMID 39745391.

• Localized (stage I–II). Standard care: wide excision, with or without sentinel lymph node biopsy. This approach is rarely used at this stage.
• Locally advanced (stage III). Standard care: adjuvant nivolumab, pembrolizumab, or dabrafenib plus trametinib. Added here, in selected high-risk cases only, alongside that care.
• Metastatic (stage IV). Standard care: Opdualag first line, nivolumab plus ipilimumab, BRAF/MEK inhibitors for V600-mutant disease; T-VEC for accessible unresectable lesions; RP1 with nivolumab after anti-PD-1.
• After Opdualag or BRAF-directed therapy. Progression after the immune-active and targeted lines. Added here, under physician review: ablation plus multi-agent intratumoral immunotherapy, aiming to re-engage the immune response at the resistant site.

WCI's stated candidacy criteria. Metastatic melanoma progressing on Opdualag, nivolumab plus ipilimumab, or single-agent checkpoint therapy · BRAF V600-mutant disease progressing on BRAF/MEK inhibitors, with or without immunotherapy · mucosal, acral or uveal melanoma with limited validated options · progression on an injected treatment · oligoprogressive disease on systemic therapy.

WCI's stated exclusions. Severe autoimmune disease with high flare risk · CNS-dominant progression without a CNS-directed plan · active severe infection · uncorrectable bleeding disorder · very poor performance status (ECOG 3 or worse). Each case is evaluated individually by the Williams Cancer Institute team.

Records. Imaging (PET/CT or CT; brain MRI) · biopsy reports with BRAF, NRAS, KIT, NF1, HLA type and subtype · the full list of prior immunotherapy and targeted therapy with dates · LDH. The physician confirms the list per case.

Setting. Most procedures are outpatient under conscious sedation; general anesthesia or an overnight stay is rarely required. Needle procedures take about an hour with about two hours' recovery.

Follow-up. Imaging at 6 to 8 weeks and the blood tests used for this cancer; the number of treatments is decided with the patient's physician; the patient's own oncologist is kept informed throughout.