Tick Saliva Against Equine Melanoma

A protein derived from the saliva of the Amblyomma sculptum tick has been successfully used by researchers at the Butantan Institute in São Paulo, Brazil, to treat skin cancer (melanoma) in horses.   Equine melanomas are spontaneous tumors. Unlike cutaneous melanomas in humans, those in horses are encapsulated and locally confined, rarely causing metastases. However, in horses, as in humans, these tumors are potentially immunogenic—that is, capable of eliciting an immune response. They are therefore useful for understanding the immune mechanisms involved in tumor regression induced by therapeutic molecules. For more than 10 years, Brazilian researchers have been studying Amblyomin-X, a protein found in tick saliva, for its antitumor properties. Several in vivo, in vitro, and preclinical toxicity studies have already been validated. However, the mechanisms behind this action remain a mystery. The researchers therefore set out to identify the molecular basis of its antitumor activity. Initially, the scientists treated spontaneous tumors in five horses for 30 days with intratumoral injections of Amblyomin-X. And the results are promising. While the control tumors remained the same size or grew larger, the tumors treated with Amblyomin-X shrank. Remission was even observed up to two months after the end of treatment, and none of the five treated animals developed any adverse effects. At the end of treatment, the tumors were surgically removed for histopathology. The researchers found no trace of tumor characteristics. To identify the signaling pathways and proteins modulated by the treatment of equine melanoma with Amblyomin-X, and to obtain molecular confirmation of the antitumor activity, the researchers used “omics” tools (genomics, transcriptomics, proteomics, and metabolomics). They discovered that the rapid response of the innate immune system (six hours after the injections) involves the modulation of four different pathways: TLR (Toll-like receptor), RIG-I (viral invasion sensors), OAS (2',5'-oligoadenylate synthetase and RNase L), and oncostatin-M (corresponding to the inflammatory pathway of the interleukin-6 family). These results describe the initial stages of the activation of a defense response that leads to tumor regression. By uncovering the mechanisms behind this antitumor activity, the researchers have identified new therapeutic targets.