title: Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.
abstract: Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Center of Clinical Comparative Oncology (C3O), Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: von Euler
authors.forename: Arian
authors.initials: A
authors.lastname: Sadeghi
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
authors.forename: Patricio
authors.initials: P
authors.lastname: Rivera
authors.forename: Angelica
authors.initials: A
authors.lastname: Loskog
authors.forename: Thomas
authors.initials: T
authors.lastname: Segall
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tötterman
mesh_terms: D000256:Adenoviridae; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D003230:Conjunctival Neoplasms / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D004283:Dog Diseases / Q000276:immunology / Q000628:therapy*; D004285:Dogs; D005260:Female; D005822:Genetic Vectors; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D009062:Mouth Neoplasms / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
chemical_list: D023201:CD40 Ligand; D007371:Interferon-gamma