Researchers have identified a naturally occurring protein in tick saliva that can block two distinct classes of immune signaling molecules at once, a first in the study of these parasites. Published in the journal Structure, the finding opens a new line of inquiry into treatments for diseases driven by runaway inflammation, including multiple sclerosis and certain cancers. The protein belongs to a family called evasins, small molecules ticks inject into their hosts to suppress immune responses at the bite site, and its dual activity sets it apart from every evasin characterized before. According to the new Structure report, the molecule’s ability to engage two chemokine classes simultaneously could make it a uniquely versatile template for anti-inflammatory drug design.
A Dual-Action Protein Breaks the Mold
Chemokines are small signaling proteins that direct immune cells to sites of infection or injury. They fall into two major structural classes, CC and CXC, and different diseases involve different combinations of both. Until now, every known evasin targeted only one class. The newly described evasin inhibits both CC and CXC chemokines, according to findings published in Structure by Cell Press. That dual capability matters because diseases such as MS and cancer recruit harmful immune cells through mixed chemokine signals from both classes. A single molecule that blocks both could, in theory, interrupt disease progression more efficiently than agents aimed at one class alone.
Earlier evasins were narrowly selective. Evasin-1, cloned from the salivary glands of the brown dog tick Rhipicephalus sanguineus, showed extremely high affinity for specific CC chemokines but left CXC signaling untouched. That selectivity was long assumed to be a fixed feature of the protein family. The discovery of a naturally occurring variant that crosses the CC/CXC divide rewrites that assumption, and suggests tick saliva harbors a wider pharmacological toolkit than researchers previously recognized. Structural analysis in Structure indicates that subtle rearrangements in the evasin’s binding loops allow it to accommodate chemokines with different folds, hinting that rational engineering could further tune or broaden this activity.
Why Chemokine Blocking Matters in MS
Multiple sclerosis involves waves of immune cells crossing the blood-brain barrier and attacking the myelin sheath that insulates nerve fibers. Two CXC chemokines, CXCL12 and CXCL13, are elevated in MS lesions and cerebrospinal fluid, where they drive immune cell recruitment and intrathecal immunoglobulin production, according to research published in the journal Brain. At the same time, CC chemokines such as CCL2 and CCL5 contribute to the inflammatory cascade in the central nervous system by attracting monocytes and T cells. Current MS therapies often rely on broad immunosuppression, which controls symptoms but leaves patients vulnerable to infections, malignancies, and other complications linked to long-term immune suppression.
A molecule that selectively neutralizes the specific CC and CXC chemokines fueling MS lesions could, in principle, dampen the destructive immune response without shutting down the entire immune system. That is the therapeutic logic behind the new evasin finding. Most existing monoclonal antibodies for MS target a single receptor or pathway, such as lymphocyte trafficking or B-cell depletion. A dual-class inhibitor derived from tick saliva would represent a fundamentally different approach, one that addresses the mixed chemokine environment researchers actually observe in patient tissue. Whether that translates from laboratory binding assays to clinical benefit remains an open question, and no human safety or efficacy trials have been reported. The Structure authors emphasize that any therapeutic application would require careful engineering to avoid unwanted interference with protective immune surveillance in the brain.
Tick Proteins and Cancer: Tissue Factor and Beyond
The cancer connection runs through a different mechanism. Tissue factor, a protein frequently overexpressed in tumor cells, is correlated with more aggressive phenotypes and a higher risk of thrombosis. Ixolaris, a tick-derived inhibitor, prevents tissue factor signaling in glioblastoma and melanoma models. In those experiments, blocking tissue factor reduced tumor growth, angiogenesis, and metastatic potential, reinforcing the idea that tick salivary proteins can modulate not only inflammation but also the coagulation pathways tumors hijack to sustain themselves. Separate research showed that overexpression of tissue factor in Meth-A sarcoma cells increased tumor growth and blood vessel formation in mice, underscoring the central role of this pathway in cancer biology.
More recent work has tested tick saliva fractions directly against human cancer cell lines. A protein fraction from Amblyomma parvum and Rhipicephalus sanguineus significantly reduced cell viability of MDA-MB-231 breast cancer cells at high concentrations, suggesting that multiple, as-yet-unidentified components can trigger tumor cell death or growth arrest. And in 2020, a separate team reported that a protein derived from tick saliva proved effective in the treatment of equine skin cancer, with the stated goal of developing new drugs based on its activity. These findings are preclinical, and no tick-derived compound has entered formal human cancer trials. Still, the breadth of activity across tumor types and species suggests the underlying biology is worth pursuing, particularly as researchers look for agents that can both disrupt tumor-supporting inflammation and interfere with pro-coagulant signaling in the tumor microenvironment.
A Hidden Pharmacy Across Tick Species
The new dual-class evasin did not emerge from nowhere. It sits within a large and genetically diverse family of chemokine-binding proteins spread across multiple tick genera. Research published in the Journal of Biological Chemistry confirmed that evasin-like proteins are widespread across Rhipicephalus, Amblyomma, and Ixodes ticks, with multiple candidates binding chemokines at measurable affinities and inhibiting downstream signaling. These proteins are thought to have evolved to help ticks feed undetected for days by disarming the host’s early inflammatory response, but from a drug discovery perspective they form a natural library of targeted immune modulators. Some family members show narrow specificity, while others interact with broader chemokine subsets, hinting at a continuum of binding profiles that medicinal chemists could mine and refine.
A separate cataloging effort mapped the salivary-gland transcripts of Amblyomma tuberculatum, the gopher-tortoise tick, and found a striking diversity of evasin-like transcripts in that single species alone. Many of these transcripts encode proteins with predicted chemokine-binding domains but have not yet been expressed or functionally characterized. Together with the Structure study, these surveys suggest that only a fraction of the tick “pharmacy” has been explored. Systematic screening of salivary proteins across life stages and feeding conditions could reveal additional dual-action evasins or molecules that target entirely different immune pathways. However, translating such discoveries into drugs will require not only biochemical characterization but also detailed toxicology, immunogenicity testing, and strategies to produce these proteins or their derivatives at scale.
Promise, Pitfalls, and the Road Ahead
The appeal of tick-derived proteins as therapeutics lies in their evolutionary tuning. Over millions of years, ticks have optimized these molecules to be potent, selective, and effective at very low concentrations in mammalian hosts. The dual-class evasin reported in Structure exemplifies this precision, binding two chemokine families that are central to chronic inflammation while sparing many unrelated signaling pathways. In concept, such a molecule could inspire drugs for MS, inflammatory bowel disease, or even certain cancers where chemokine-driven cell trafficking sustains pathology. The same is true for anticoagulant and anti-tumor agents like Ixolaris, which leverage natural mechanisms ticks use to prevent clotting at the bite site.
Yet the pitfalls are substantial. Tick salivary proteins are foreign to the human immune system and may provoke neutralizing antibodies or allergic reactions upon repeated dosing. Their relatively large size and complex disulfide-bonded structures can complicate manufacturing and raise costs compared with small-molecule drugs. Moreover, precisely because these proteins are so effective at blunting host defenses, there is a real risk of unintended immunosuppression or bleeding if their activity is not tightly controlled. Researchers are therefore exploring strategies such as designing smaller peptide mimics, grafting key binding motifs onto human protein scaffolds, or using gene therapy vectors to deliver transient, localized expression. For now, the dual-class evasin and its cousins remain experimental tools, but as structural and functional data accumulate, they may evolve from curiosities of parasite biology into blueprints for a new generation of targeted anti-inflammatory and anticancer therapies.
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*This article was researched with the help of AI, with human editors creating the final content.
