Depleting Autoreactive B‑Cells Using Targeted Photodynamic Therapy

TL;DR

This paper introduces a method to selectively destroy harmful B cells in autoimmune diseases without affecting the rest of the immune system.

Contribution

A targeted photodynamic therapy approach using a dimeric peptidic antigen and photosensitizer to selectively eliminate autoreactive B cells.

Findings

The construct selectively eliminates autoreactive B cells after light exposure.

The treatment is not cytotoxic to cells lacking the autoreactive BCR.

Minimal impact on untargeted cells in a 3D coculture model was observed.

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.

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