Saellstrom Sara, Sadeghi Arian, Eriksson Emma, Segall Thomas, Dimopoulou Maria, Korsgren Olle, Loskog Angelica Si, Tötterman Thomas H, Hemminki Akseli, Ronnberg Henrik
University Animal Hospital, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Front Vet Sci. 2021 Jul 23;8:695222. doi: 10.3389/fvets.2021.695222. eCollection 2021.
Malignant melanoma is a serious disease in both humans and dogs, and the high metastatic potential results in poor prognosis for many patients. Its similarities with human melanoma make spontaneous canine melanoma an excellent model for comparative studies of novel therapies and tumor biology. Gene therapy using adenoviruses encoding the immunostimulatory gene CD40L (AdCD40L) has shown promise in initial clinical trials enrolling human patients with various malignancies including melanoma. We report a study of local AdCD40L treatment in 32 cases of canine melanoma (23 oral, 5 cutaneous, 3 ungual and 1 conjunctival). Eight patients were World Health Organization (WHO) stage I, 9 were stage II, 12 stage III, and 3 stage IV. One to six intratumoral injections of AdCD40L were given every seven days, combined with cytoreductive surgery in 20 cases and only immunotherapy in 12 cases. Tumor tissue was infiltrated with T and B lymphocytes after treatment, suggesting immune stimulation. The best overall response based on result of immunotherapy included 7 complete responses, 5 partial responses, 5 stable and 2 progressive disease statuses according to the World Health Organization response criteria. Median survival was 285 days (range 20-3435 d). Our results suggest that local AdCD40L therapy is safe and could have beneficial effects in dogs, supporting further treatment development. Clinical translation to human patients is ongoing.
恶性黑色素瘤在人类和犬类中都是一种严重的疾病，其高转移潜能导致许多患者预后不良。它与人类黑色素瘤的相似性使得自发性犬类黑色素瘤成为新型疗法和肿瘤生物学比较研究的理想模型。使用编码免疫刺激基因CD40L的腺病毒（AdCD40L）进行基因治疗在纳入包括黑色素瘤在内的各种恶性肿瘤患者的初步临床试验中显示出前景。我们报告了一项对32例犬类黑色素瘤（23例口腔、5例皮肤、3例爪部和1例结膜）进行局部AdCD40L治疗的研究。8例患者为世界卫生组织（WHO）I期，9例为II期，12例为III期，3例为IV期。每7天进行1至6次瘤内注射AdCD40L，20例联合减瘤手术，12例仅进行免疫治疗。治疗后肿瘤组织中有T和B淋巴细胞浸润，提示免疫刺激。根据世界卫生组织的反应标准，基于免疫治疗结果的最佳总体反应包括7例完全缓解、5例部分缓解、5例病情稳定和2例病情进展。中位生存期为285天（范围20 - 3435天）。我们的结果表明，局部AdCD40L治疗是安全的，对犬类可能有有益效果，支持进一步的治疗开发。向人类患者的临床转化正在进行中。
