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Research article - Peer-reviewed, 2021

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

Saellstrom, Sara; Sadeghi, Arian; Eriksson, Emma; Segall, Thomas; Dimopoulou, Maria; Korsgren, Olle; Loskog, Angelica SI.; Totterman, Thomas H.; Hemminki, Akseli; Ronnberg, Henrik

Abstract

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.

Keywords

immuno oncology; adenoviral vectors; translational medicine; canine malignant melanoma; clinical trials; AdCD40L

Published in

Frontiers in Veterinary Science
2021, volume: 8, article number: 695222
Publisher: FRONTIERS MEDIA SA

Authors' information

Swedish University of Agricultural Sciences, University Animal Hospital
Sadeghi, Arian
Uppsala University
Eriksson, Emma
Uppsala University
Segall, Thomas
National Veterinary Institute SVA
Swedish University of Agricultural Sciences, University Animal Hospital
Korsgren, Olle
Uppsala University
Loskog, Angelica SI.
Uppsala University
Totterman, Thomas H.
Uppsala University
Hemminki, Akseli
University of Helsinki
Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Clinical Science

Publication Identifiers

DOI: https://doi.org/10.3389/fvets.2021.695222

URI (permanent link to this page)

https://res.slu.se/id/publ/113140