BAFF Plus Models for Systemic Lupus Erythematosus (SLE)

The BAFF PLUS portfolio from GemPharmatech represents a significant advancement over conventional systemic lupus erythematosus (SLE) models by integrating spontaneous lupus pathology with fully humanized T‑cell and B‑cell therapeutic targets. This dual approach addresses two critical limitations of traditional murine SLE systems: inadequate clinical translatability and inconsistent disease progression.

Mechanistically, BAFF overexpression drives sustained B‑cell hyperactivation, recapitulating the hallmark immune dysregulation observed in human SLE. These mice develop progressive lupus nephritis, elevated anti‑dsDNA antibody titers, and polyclonal B‑cell expansion—phenotypes that closely mirror the human autoimmune pathology and provide a robust platform for evaluating B‑cell‑directed interventions.

Key Features & Scientific Utility

• Clinically Relevant Pathology: Persistent BAFF-driven B‑cell activation, spontaneous autoantibody production, and immune complex‑mediated glomerulonephritis ensure disease stability and reproducibility across studies.

• Fully Humanized Targets: When crossed with strains expressing human CD3, CD19, CD20, or BCMA, the BAFF PLUS platform enables preclinical assessment of CD3‑based T‑cell engagers (TCEs) within an immunocompetent lupus microenvironment.

• Comprehensive Endpoint Assessment: Researchers can simultaneously evaluate:

  1. Therapeutic efficacy (B‑cell depletion, autoantibody reduction, renal function)

  2. Cytokine activation profiles and cytokine release syndrome (CRS) risk

  3. Long‑term safety and tolerability in the context of chronic inflammation

This integrated model system supports more clinically predictive evaluation of bispecific antibodies, TCEs, and other immunomodulatory candidates for autoimmune indications.

Available BAFF PLUS Models

Case Study

Teclistamab significantly alleviates the SLE-like phenotype in BALB/c-hBAFF/hCD3/hBCMA mice after 2 and 4 weeks of treatment.

(A) Study design for a spontaneous SLE model in 12- to 16-week-old BALB/c-hBAFF/hCD3/hBCMA mice.

(B) ELISA for serum mIgG, mIgM and anti-dsDNA secretion levels in 12- to 16-week-old BALB/c-hBAFF/hCD3/hBCMA mice;

(C-D) Flow cytometry analysis of plasma cell and hBCMA⁺ plasma cell proportions and cell numbers in blood after (C) 2 weeks and (D) 4 weeks of Teclistamab treatment.

Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; analyzed by one-way ANOVA.