Protein from tick saliva shows promise against horse melanomas

A protein derived from tick saliva is effective in the treatment of skin cancer in horses, according to scientists.

Researchers at the Butantan Institute in São Paulo, Brazil, have described in the journal Scientific Reports how they used the protein to treat melanomas.

Their work centered on five animals with spontaneous skin tumors.

The protein, found in the saliva of the tick Amblyomma sculptum, is Amblyomin-X.

The principal researcher in the study is Ana Marisa Chudzinski-Tavassi, who heads the Center of Excellence in New Target Discovery, an engineering research center at the Butantan Institute.

Amblyomin-X has been studied at the institute for more than 10 years and evidence has emerged that it has significant anti-tumor potential in the laboratory. It has also delivered promising results when its toxicity in living animals was assessed.

Equine melanomas are spontaneous tumors.

Unlike cutaneous melanomas in humans, they tend to be encapsulated in horses and locally confined, rarely spreading elsewhere.

However, in both humans and horses, these tumors are potentially immunogenic — that is, capable of producing an immune response. This means they can serve as a model for the investigation of the immune mechanisms involved in tumor regression induced by therapeutic molecules.

In the first phase of the study, spontaneous tumors in five horses were treated for 30 days with injections of Amblyomin-X into the tumors.

The treatment took place at the Butantan Institute’s farm in Araçariguama, in São Paulo state.

The animals were clinically monitored throughout the treatment, with blood work and biochemical laboratory tests.

The results were promising. Control tumors — those not treated with the compound — maintained their shape and grew in size, whereas tumors treated with Amblyomin-X shrank and, in some cases, even reached remission up to two months after treatment ended.

None of the five treated animals developed any adverse reactions. At the end of the treatment, the tumors were surgically removed for histopathological analysis. The researchers found no trace of tumoral characteristics.

The researchers used “omics” tools (genomics, transcriptomics, proteomics and metabolomics) to analyze the signaling pathways and proteins affected by the treatment of horse melanomas with Amblyomin-X.

Roger Chammas, a researcher at the São Paulo State Cancer Institute (ICESP), collaborated with scientists at the center on the project.

The results, published by the group between 2010 and 2017, suggest that the anti-tumor action of Amblyomin-X occurred via the modulation of the endoplasmic reticulum and mitochondrial stress and apoptotic and proteasomic pathways, among others.

The transcriptome study was expected to confirm activation of these pathways and show whether others were affected by the treatment.

The researchers also deployed next-generation sequencing and analysis based on bioinformatics and systems biology to map the initial mechanisms of the response triggered by Amblyomin-X, which culminated in tumor regression.

Among the findings of the transcriptomic analysis was the discovery that the innate immune system’s rapid response (six hours after the injections) involved 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 interleukin-6 family inflammation pathway).

These findings described the first steps in the activation of a defense response that culminated in tumor regression, pointing to potential candidate targets for therapies against tumors.