Adenoviral CD40 Ligand Immunotherapy in 32 Canine Malignant Melanomas-Long-Term Follow Up.

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.

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Copyright © 2021 Saellstrom, Sadeghi, Eriksson, Segall, Dimopoulou, Korsgren, Loskog, Tötterman, Hemminki and Ronnberg.

Déclaration de conflit d'intérêts

AH is a shareholder in Targovax ASA. AH is an employee and shareholder in TILT Biotherapeutics Ltd. AL is the CEO of Lokon Pharma AB, a shareholder of Lynxalo AB, a board member of Lokon Pharma AB, Vivolux AB, Repos Pharma AB, Tanea Medical AB, Bioimics AB, Lynxalo AB and an alternate board member of Nexttobe AB, Almoalo AB, Promegranate Veterinary AB and Aros Biotech AB. Further, AL has a royalty agreement with Alligator Bioscience AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.