Intralesional and intratumoral therapies in melanoma: current evidence and future perspectives—a narrative review
- 1Dermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain
- 2Network Biomedical Research Center on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
- 3Medical Oncology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain
Abstract
Background and Objective: Immune checkpoint inhibitors and B-Raf proto-oncogene (BRAF)/mitogen-activated protein kinase kinase (MEK)-targeted therapies have transformed the treatment of advanced melanoma, yet treatment resistance and the need for additional locoregional control remain clinical challenges. Intralesional and intratumoral therapies constitute an expanding therapeutic field, with numerous agents under investigation. Approved options include two oncolytic viruses: talimogene laherparepvec (T-VEC) as monotherapy and RP1 combined with nivolumab. This narrative review aims to summarize the current landscape of these therapies, including their mechanisms of action, clinical efficacy, safety, and ongoing development, and to contextualize their role within contemporary melanoma treatment strategies.
Methods: PubMed/MEDLINE and Google Scholar were searched for English-language literature published between January 1, 2000, and August 30, 2026, using terms related to melanoma and intralesional or intratumoral therapies. ClinicalTrials.gov was searched to identify ongoing trials.
Key Content and Findings: Therapeutic platforms include oncolytic viruses, cytokine-based therapies, antibody-cytokine fusion proteins, Toll-like receptor agonists, intratumoral checkpoint inhibitors, RNA-based approaches, and other local strategies. Their use is being studied across different clinical settings, both as monotherapy and in combination with systemic immunotherapy. Intralesional therapies may improve locoregional control in selected patients with a partial response or oligoprogression during systemic treatment. Progression with a high visceral tumor burden may represent a less favorable setting for a predominantly intralesional approach. Neoadjuvant applications are also under investigation. Strengths include high local drug exposure with the potential to limit systemic toxicity, modulation of the tumor microenvironment to support combinations with immune checkpoint inhibitors, and responses in non-injected lesions with selected agents. Limitations include the need for accessible lesions, procedure-related burden, and the early stages of clinical development of many agents, with limited comparative evidence.
Conclusions: Intralesional and intratumoral therapies offer additional treatment options for selected patients with melanoma, but their integration into current treatment algorithms remains incompletely defined. Comparative trials, refinement of patient selection, and prospective validation of biomarkers are needed to establish which patients are most likely to benefit.
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BibTeX
@article{hernandezsantacana2026intralesional,
title = {{Intralesional and intratumoral therapies in melanoma: current evidence and future perspectives—a narrative review}},
author = {Marc Hernández-Santacana and Claudia Guilarte-Cadavide and Maria Ayguasanosa-Àvila and Pablo Balado-Simó and Laura Serra-García and Paula Aguilera-Peiró and Víctor Albarrán-Fernández and Mario Balsa and Ariadna Ortiz-Brugués and Sebastian Podlipnik and Ana Arance and Cristina Carrera and Susana Puig and Josep Malvehy},
journal = {Annals of Translational Medicine},
year = {2026},
month = oct,
doi = {10.21037/atm-2026-0175},
url = {https://doi.org/10.21037/atm-2026-0175},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Intralesional and intratumoral therapies in melanoma: current evidence and future perspectives—a narrative review
AU - Marc Hernández-Santacana
AU - Claudia Guilarte-Cadavide
AU - Maria Ayguasanosa-Àvila
AU - Pablo Balado-Simó
AU - Laura Serra-García
AU - Paula Aguilera-Peiró
AU - Víctor Albarrán-Fernández
AU - Mario Balsa
AU - Ariadna Ortiz-Brugués
AU - Sebastian Podlipnik
AU - Ana Arance
AU - Cristina Carrera
AU - Susana Puig
AU - Josep Malvehy
PY - 2026
DA - 2026/10/23
JO - Annals of Translational Medicine
DO - 10.21037/atm-2026-0175
UR - https://doi.org/10.21037/atm-2026-0175
AB - Background and Objective: Immune checkpoint inhibitors and B-Raf proto-oncogene (BRAF)/mitogen-activated protein kinase kinase (MEK)-targeted therapies have transformed the treatment of advanced melanoma, yet treatment resistance and the need for additional locoregional control remain clinical challenges. Intralesional and intratumoral therapies constitute an expanding therapeutic field, with numerous agents under investigation. Approved options include two oncolytic viruses: talimogene laherparepvec (T-VEC) as monotherapy and RP1 combined with nivolumab. This narrative review aims to summarize the current landscape of these therapies, including their mechanisms of action, clinical efficacy, safety, and ongoing development, and to contextualize their role within contemporary melanoma treatment strategies. Methods: PubMed/MEDLINE and Google Scholar were searched for English-language literature published between January 1, 2000, and August 30, 2026, using terms related to melanoma and intralesional or intratumoral therapies. ClinicalTrials.gov was searched to identify ongoing trials. Key Content and Findings: Therapeutic platforms include oncolytic viruses, cytokine-based therapies, antibody-cytokine fusion proteins, Toll-like receptor agonists, intratumoral checkpoint inhibitors, RNA-based approaches, and other local strategies. Their use is being studied across different clinical settings, both as monotherapy and in combination with systemic immunotherapy. Intralesional therapies may improve locoregional control in selected patients with a partial response or oligoprogression during systemic treatment. Progression with a high visceral tumor burden may represent a less favorable setting for a predominantly intralesional approach. Neoadjuvant applications are also under investigation. Strengths include high local drug exposure with the potential to limit systemic toxicity, modulation of the tumor microenvironment to support combinations with immune checkpoint inhibitors, and responses in non-injected lesions with selected agents. Limitations include the need for accessible lesions, procedure-related burden, and the early stages of clinical development of many agents, with limited comparative evidence. Conclusions: Intralesional and intratumoral therapies offer additional treatment options for selected patients with melanoma, but their integration into current treatment algorithms remains incompletely defined. Comparative trials, refinement of patient selection, and prospective validation of biomarkers are needed to establish which patients are most likely to benefit.
SN - 2305-5839
SN - 2305-5847
ER -