New Antibody Targets BAMBI to Rewire Immune Cells in Psoriatic Arthritis

Psoriasis and its joint-destroying companion, psoriatic arthritis, affect hundreds of millions of people worldwide, and a substantial fraction of patients fail to respond to the biologics currently on the market. A team of researchers from Inhibitec Anticuerpos, the University of Cantabria, the Institute of Biomedicine and Biotechnology of Cantabria, and IDIVAL in Spain now reports a fresh attack on this problem: a humanized monoclonal antibody called hB101.37 that blocks a membrane protein known as BAMBI, short for BMP and Activin Membrane-Bound Inhibitor. In preclinical models of both psoriasis and psoriatic arthritis, the antibody reduced inflammatory skin and joint disease while appearing to reset, rather than simply suppress, the immune imbalance that drives the conditions. The work, published open access in the Journal of Translational Medicine, positions BAMBI inhibition as a first-in-class strategy with a mechanism of action that no approved therapy currently exploits.

To understand why the target is unusual, it helps to look at the immunology of the disease. Psoriasis is a chronic autoimmune skin disorder affecting roughly two percent of the global population, and about thirty percent of those patients go on to develop psoriatic arthritis, a condition that combines joint inflammation, pain, and progressive structural damage. Both diseases are driven primarily by CD4-positive T cells, the immune cells whose fate is dictated by the cytokine environment they encounter. One of the most influential of these signals is TGF-beta, a molecule with a famously dual personality: it can push naive T cells toward Th17 cells, potent drivers of inflammation, or toward regulatory T cells, or Tregs, which restrain autoimmunity and protect tissue. In psoriasis and psoriatic arthritis, this balance tips sharply toward Th17 cells, while the protective regulatory arm underperforms.

Most existing therapies attack the downstream consequences of that imbalance rather than the balance itself. Tumor necrosis factor inhibitors and antibodies against the IL-17 axis have transformed treatment for many patients, but the study’s authors note that roughly thirty-five to forty percent of people with psoriatic arthritis fail to reach a minimum level of efficacy with these drugs, and resistance emerges over time in others. Blocking BAMBI offers a conceptually different approach. BAMBI is a pseudoreceptor, a membrane-bound protein that lacks an intracellular signaling domain and acts as a decoy that modulates signaling by the TGF-beta and related pathways. By inhibiting BAMBI with an antibody, the researchers aimed to enhance the signaling that favors regulatory T cell differentiation, thereby rebuilding the immune system’s own brakes instead of merely blocking its accelerators.

The antibody itself, hB101.37, is a humanized monoclonal antibody, meaning its protein framework has been engineered to resemble human antibodies closely enough to minimize the risk that a patient’s immune system will reject it as foreign. The team evaluated its therapeutic effect in three preclinical mouse models: an imiquimod-induced model of psoriasis, an IL-21-induced model of the skin disease, and a mannan-induced model of psoriatic arthritis. These models reproduce key features of the human conditions, from scaly skin inflammation to joint swelling, and are standard tools for testing whether a candidate biologic can plausibly work in patients before any clinical trial begins.

The results were striking on several fronts. Treatment with hB101.37 reduced disease in both the psoriasis and psoriatic arthritis models, confirming efficacy across the spectrum of the disease. Flow cytometry analyses of immune cells from treated animals showed that the antibody reduced the population of pro-inflammatory Th17 cells while promoting differentiation toward the regulatory T cell lineage, exactly the rebalancing effect the researchers had predicted from the mechanism. In molecular terms, the team traced the effect to activation of the Smad2/3 pathway, the canonical intracellular signaling route downstream of the TGF-beta receptor, which they assessed by western blot. In other words, blocking the decoy receptor BAMBI allowed the genuine TGF-beta signal to flow more freely into the Smad pathway, steering T cell fate toward tolerance.

Perhaps the most commercially and clinically significant comparison in the study is head-to-head with an established drug class. The researchers report that anti-BAMBI therapy showed potentially greater clinical efficacy in psoriasis than anti-IL-17A monoclonal antibodies, one of the most successful modern treatments for the disease. If that advantage translates to humans, it would represent a meaningful advance for the many patients whose disease is incompletely controlled by IL-17 blockade. Because the antibody works upstream of the IL-17 axis, reshaping the T cell populations that generate inflammatory cytokines in the first place, it could also, in principle, address multiple inflammatory pathways simultaneously rather than a single mediator.

Safety is where many promising immunomodulators stumble, and the Spanish team devoted considerable effort to characterizing the antibody’s preclinical safety profile. They performed histological and immunofluorescence analyses of murine tissues, measured inflammatory markers by ELISA and gene expression by quantitative PCR, and, notably, conducted transthoracic echocardiography after chronic administration of the antibody to assess cardiac function. Cardiac monitoring matters because TGF-beta family signaling is implicated in fibrosis and remodeling in multiple organs, so any therapy that perturbs this pathway must demonstrate that it does not provoke cardiovascular or structural toxicity. According to the authors, the preclinical phase confirmed the safety profile of the therapeutic antibody, an essential green light for moving toward clinical development.

The work also extended beyond mice. The researchers examined the effects of hB101.37 on human CD4-positive T cells in vitro, isolating the cells from buffy coat samples of anonymous healthy donors provided by the Blood and Tissue Bank of Cantabria under ethics committee approval. Demonstrating that the antibody can modulate T cell differentiation in human cells, not just in engineered mouse models, strengthens the translational case considerably, since species differences in cytokine biology frequently derail therapies that look spectacular in rodents. The animal studies were conducted under the approval of the University of Cantabria’s Institutional Laboratory Animal Care and Use Committee and in accordance with European directives on animal welfare.

The research is the product of a collaboration that blends a small biotechnology company with academic immunology groups. Inhibitec Anticuerpos, based in Santander, developed the antibody, and several of its scientists are coauthors, while the University of Cantabria’s molecular biology and pharmacology departments and the CSIC-affiliated biomedicine institute contributed the disease models and mechanistic analyses. The work was funded by a constellation of Spanish public agencies, including the Centro para el Desarrollo Tecnológico Industrial, the Ministry of Science, Innovation and Universities, SODERCAN, and the Government of Cantabria, along with the United States National Psoriasis Foundation, reflecting the international interest in new psoriasis therapeutics. The authors note a conflict of interest: Ramón Merino is a cofounder and stockholder of Inhibitec, and several coauthors are company employees, with the company holding a license for a patent application covering monoclonal antibodies against BAMBI for inflammatory diseases.

Caveats remain. The findings are preclinical, generated in mouse models and human cells in culture, and the antibody has not yet been tested in patients, where questions of dosing, immunogenicity, long-term safety, and real-world efficacy will ultimately be decided. The published version of the paper was shared early as an accepted manuscript and remains subject to final editorial edits. Still, the study offers something the psoriasis field has lacked: a genuinely new point of intervention that does not simply block another inflammatory cytokine but instead reprograms the T cell balance itself, boosting the regulatory arm of immunity while shrinking the inflammatory one. For the large minority of patients with psoriatic arthritis who do not respond to TNF or IL-17 blockers, and for whom drug resistance looms over even successful treatments, a first-in-class antibody that teaches the immune system to regulate itself is a development worth watching closely as it advances toward the clinic.

Subject of Research: Development of a humanized anti-BAMBI monoclonal antibody for the treatment of psoriasis and psoriatic arthritis

Article Title: Humanized anti-BAMBI monoclonal antibody as a novel therapeutic strategy for psoriatic arthritis

Article References: Perez-Adrian, P., Romero, D., Cappitelli, V., Gallego, F., Ruso-Julve, F., Calvo, M., Garcia, R., Puyalto, A., Gomez, I., Merino, D., Gil-de-Gomez, L., Merino, R., & Casado-Medrano, V. (2026). Humanized anti-BAMBI monoclonal antibody as a novel therapeutic strategy for psoriatic arthritis. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-09038-5

Image Credits: AI Generated

DOI: 10.1186/s12967-026-09038-5

Keywords: psoriasis, psoriatic arthritis, BAMBI, monoclonal antibody, Th17 cells, regulatory T cells, TGF-beta, immunotherapy, biologics, Smad2/3 pathway, preclinical models, autoimmune disease