Depleting Autoreactive B-Cells Using Targeted Photodynamic Therapy

ACS Pharmacology & Translational Science, vol. 8, pp. 3523–3530

Abstract

In many autoimmune pathologies, including Rheumatoid Arthritis (RA), only a small percentage of the total B cell population is autoreactive and sustain disease. Yet, current immunotherapy treatments often eliminate the entire B-cell population, leading to immune deficiency. We developed an approach to selectively eliminate autoreactive B cells with targeted photodynamic therapy (tPDT). We designed a construct containing a dimeric peptidic antigen (diCCP4) that selectively binds a patient-derived autoreactive B cell receptor (BCR) and additionally included the photosensitizer IRDye700DX. We tested the construct on a modified Ramos B-cell line (Ramos 3F3), expressing this specific autoreactive BCR sequence. After brief exposure to 689 nm light, the photosensitizer selectively eliminates the modified Ramos cells, while the construct is not cytotoxic to cells lacking the autoreactive BCR. In a 3D coculture of the Ramos autoreactive B cell line with peripheral blood mononuclear cells (PBMCs) we observed only a minimal response of the untargeted cells. These results highlight the potential of tPDT against autoreactive B cells in autoimmune disease.

Authors 4

1. Kevin R. Venrooij

   Radboud University Nijmegen

   Affiliation as printed

   Institute of Molecules and Materials, Synthetic Organic Chemistry, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

2. Theodoros Ioannis Papadimitriou

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Rheumatology, Radboudumc, Geert Grooteplein Zuid 8, Nijmegen 6525GA, The Netherlands

3. Daphne N. Dorst

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Rheumatology, Radboudumc, Geert Grooteplein Zuid 8, Nijmegen 6525GA, The Netherlands

   Institute of Molecules and Materials, Synthetic Organic Chemistry, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

4. Kimberly M. Bonger corresponding Aachen Leiden Institute for Chemistry, Chemical Biology & Immunology

   Leiden University · Radboud University Nijmegen

   Affiliation as printed

   Institute of Molecules and Materials, Synthetic Organic Chemistry, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

   Leiden University, Leiden Institute for Chemistry, Chemical Biology & Immunology, Einsteinweg 55, CC Leiden 2333, The Netherlands