Langerhans Cell Histiocytosis (LCH) is a rare clonal disorder that has the abnormal proliferation and accumulation of Langerhans-like cells, which belong to the dendritic cell family and express CD1a+/CD207+ (langerin+) markers. Protheragen offers specialized comprehensive preclinical development services for LCH, extending from target validation through therapeutic development.
Langerhans Cell Histiocytosis (LCH) is an uncommon myeloid neoplastic condition which emerges due to the clonal expansion of CD1a+/CD207+ dendritic cells forming granulomatous lesions in skin, bones, and visceral organs. It leads to erythematous scaly papules as well as ulcerations with systemic inflammation. Incidence is 4-9 per million children and 1–2 per million adults, with high relapse rates and organ-specific morbidity under treatment. The condition is driven by mutations within the MAPK pathway resulting in its prominent symptoms.
LCH is fundamentally a clonal disorder due mostly to somatic activating mutations in the MAPK signaling pathways such as BRAF V600E. Such changes result in unrestrained growth and persistence of Langerhans-like cells forming tumors, infiltrating different organs, producing tissues rich in pro-inflammatory cytokines responsible for chronic inflammation and subsequent damage leading further exacerbation of injury causing disease symptoms.
Fig.1 Cellular Interaction in Langerhans Cell Histiocytosis. (Goyal et al., 2022)| Therapeutic Strategy | Target / Intervention | Mechanistic Validation/Model Data | Development Stage |
| Dabrafenib | BRAFV600E inhibitor | Suppresses ERK phosphorylation in CD207+ progenitors; rapid relapse post-cessation | Approved |
| Trametinib | MEK1/2 inhibitor | Reduces neurodegeneration in BRAFWT CNS-LCH models; superior CNS penetration | Phase II/III |
| Cobimetinib | MEK inhibitor | Mitigates hyperkeratotic rash in BRAFV600E murine models when combined with dabrafenib | Phase II |
| Anti-SIRPα mAb | CD47-SIRPα "don't eat me" blockade | >80% LCH cell clearance via enhanced macrophage phagocytosis in BM xenografts | Phase I |
| Spesolimab | IL-36R antagonist | Theoretical rationale (IL-36γ+ in granulomas); no LCH-specific data | Phase II exploratory |
| PD-1 inhibitors | Immune checkpoint blockade | Induced LCH regression in melanoma comorbidity cases; modulates TREG infiltration | Case reports |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Protheragen is a full-service provider committed to advancing therapies for Langerhans Cell Histiocytosis. Our team of expert scientists, dermatologists, and geneticists leverage cutting-edge technologies to drive progress in LCH, with a focus on therapeutic development, diagnostics development as well as disease model development services to support your projects.
In Vivo Pharmacokinetics Services
As a one-stop preclinical partner, Protheragen accelerates transformative therapies for high-risk cutaneous neoplasms like Langerhans cell histiocytosis. Our integrated solutions advance targets from disease modeling to drug safety evaluation and DMPK services—delivering actionable insights for relapsed cases.
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