Recognition of Antigen-Specific B-Cell Receptors from Chronic Lymphocytic Leukemia Patients by Synthetic Antigen Surrogates

• A protocol is developed to identify ligands for antigen-specific B cell receptors
• Dextran-ligand conjugates can bind to native, antigen-specific B cells
• Pathogenic B cells from CLL patients can be targeted selectively

SummaryIn patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates.

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