Engineering Chimeric Autoantibody Receptor T Cells for Targeted B Cell Depletion in Multiple Sclerosis Model: An In-Vitro Study Publisher



Sahlolbei M^{1, 2} ; Azangoukhyavy M³ ; Khanali J³ ; Khorsand B^{4, 5} ; Shiralipour A⁶ ; Ahmadbeigi N⁷ ; Madjd Z² ; Ghanbarian H⁶ ; Ardjmand A⁸ ; Hashemi SM^{9, 10} ; Kiani J^{1, 2}
Source: Heliyon Published:2023

Abstract

Background: Recent evidence suggests that B cells and autoantibodies have a substantial role in the pathogenesis of Multiple sclerosis. T cells could be engineered to express chimeric autoantibody receptors (CAARs), which have an epitope of autoantigens in their extracellular domain acting as bait for trapping autoreactive B cells. This study aims to assess the function of designed CAAR T cells against B cell clones reactive to the myelin basic protein (MBP) autoantigen. Methods: T cells were transduced to express a CAAR consisting of MBP as the extracellular domain. experimental autoimmune encephalomyelitis (EAE) was induced by injecting MBP into mice. The cytotoxicity, proliferation, and cytokine production of the MBP-CAAR T cells were investigated in co-culture with B cells. Results: MBP-CAAR T cells showed higher cytotoxic activity against autoreactive B cells in all effector-to-target ratios compared to Mock T cell (empty vector-transduced T cell) and Un-T cells (un-transduced T cell). In co-cultures containing CAAR T cells, there was more proliferation and inflammatory cytokine release as compared to Un-T and Mock T cell groups. Conclusion: Based on these findings, CAAR T cells are promising for curing or modulating autoimmunity and can be served as a new approach for clone-specific B cell depletion therapy in multiple sclerosis. © 2023 The Authors