II-Targeted Nanobody-Based Therapy for Multiple Sclerosis

Authors:

Ella Borgman, Camille Le Gall, Novalia Pishesha

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

We have developed a nanobody-based therapy to induce antigen- a small molecule anti-inflammatory drug, this trimodal construct specific tolerance in multiple sclerosis (MS). The MS therapy (VHH MHCII-MOG-DEX) effectively halted and reversed the involves a small antibody fragment, called a nanobody, that severity of EAE. We are currently investigating the mechanisms recognizes class II major histocompatibility complex antigens that explain the efficacy of this nanobody-based therapy. One (VHH MHCII), conjugated to myelin associated proteins (e.g. major aim is to understand the therapeutic’s influence on the myelin oligodendrocyte glycoprotein (MOG)). MHC II is interaction between T-cells and APCs. Using maleimide-thiol expressed by antigen presenting cells (APCs). When professional click chemistry and the theory of uLIPSTIC (universal labelling antigen presenting cells such as macrophages and dendritic of immune partnerships by SorTagging intercellular contacts), cells encounter antigen under non-inflammatory conditions, we have developed an ex vivo strategy, to look at immune cell they are tolerogenic. Therefore, if MS-associated peptides are interactions. Elucidating the treatment’s mechanism of action will delivered to APCs, antigen-specific tolerance should be induced. enable further modification and improvement of MS treatments, The lab has previously demonstrated that a single dose of and translation to other autoimmune diseases. Additionally, such VHH MHCII-MOG provides enduring protection from induction mechanistic studies will provide insight on whether this treatment of experimental autoimmune encephalitis (EAE), a MS mouse approach could be successfully applied clinically. model. When VHH -MOG was conjugated to dexamethasone, MHCII

Abstract:

We have developed a nanobody-based therapy to induce antigen- a small molecule anti-inflammatory drug, this trimodal construct specific tolerance in multiple sclerosis (MS). The MS therapy (VHH MHCII-MOG-DEX) effectively halted and reversed the involves a small antibody fragment, called a nanobody, that severity of EAE. We are currently investigating the mechanisms recognizes class II major histocompatibility complex antigens that explain the efficacy of this nanobody-based therapy. One (VHH MHCII), conjugated to myelin associated proteins (e.g. major aim is to understand the therapeutic’s influence on the myelin oligodendrocyte glycoprotein (MOG)). MHC II is interaction between T-cells and APCs. Using maleimide-thiol expressed by antigen presenting cells (APCs). When professional click chemistry and the theory of uLIPSTIC (universal labelling antigen presenting cells such as macrophages and dendritic of immune partnerships by SorTagging intercellular contacts), cells encounter antigen under non-inflammatory conditions, we have developed an ex vivo strategy, to look at immune cell they are tolerogenic. Therefore, if MS-associated peptides are interactions. Elucidating the treatment’s mechanism of action will delivered to APCs, antigen-specific tolerance should be induced. enable further modification and improvement of MS treatments, The lab has previously demonstrated that a single dose of and translation to other autoimmune diseases. Additionally, such VHH MHCII-MOG provides enduring protection from induction mechanistic studies will provide insight on whether this treatment of experimental autoimmune encephalitis (EAE), a MS mouse approach could be successfully applied clinically. model. When VHH -MOG was conjugated to dexamethasone, MHCII

Source:

Harvard / DecodingAntigen-SpecificToleranceMechanismsImposedbyanMHCClass / 2025

Topics:

antigen, nanobody, therapy, vhh, mhcii, cell, apcs, treatment, multiple, sclerosi, developed, small

Co-authors:

@ellaborgman255 , @camillelegall256 , @novaliapishesha257