Translating B-Cell and Plasma-Cell Targeting from Oncology to Autoimmunity: Modalities, Quantitative Bridging, and a...

Area of Science:

• Immunology
• Oncology
• Rheumatology

Background:

• B cells are implicated in malignancies and autoimmune diseases via autoantibody production, antigen presentation, and cytokine dysregulation.
• Pathogenic B-cell or plasma-cell persistence drives disease, with varying dominant compartments across autoimmune conditions.

Purpose of the Study:

• To synthesize the biological rationale for B-cell-axis targeting in oncology and autoimmunity.
• To propose a pathobiological framework for B-cell-mediated diseases.
• To outline and compare B-cell-targeting modalities and their application in autoimmune archetypes.

Main Methods:

• Review of mechanisms, lineage coverage, depletion depth, durability, and tolerability of CD20-, CD19-, CD38-, and BCMA-directed antibodies, bispecific T-cell engagers, and CAR T cells.
• Comparison of dosing paradigms, PK/PD, exposure-response relationships, and safety trade-offs between oncology and autoimmunity.
• Mapping of therapeutic modalities onto biologically defined autoimmune archetypes.

Main Results:

• Therapies developed for lymphoma and myeloma are being repurposed for autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and lupus erythematosus.
• Pivotal translational inflection points include rituximab's extension beyond lymphoma and approvals in neuroimmunology.
• Plasma cell-directed and T-cell-engaging strategies offer deep immune resets for refractory diseases.

Conclusions:

• A model-informed roadmap is proposed to optimize B-cell-targeting therapy selection, patient enrichment, and dose/regimen design.
• Biomarker-guided retreatment, infection-risk mitigation, and regimen adaptation are emphasized for non-malignant diseases.
• Extrapolation of treatment strategies from oncology to autoimmunity requires careful consideration of PK/PD and safety profiles.