Autologous T-Cell Vaccination for Multiple Sclerosis

Abstract

T-cell vaccination (TCV) is a unique approach to induce immune regulation that may have importance in the treatment of autoimmune diseases, including multiple sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated form of the disease-causing agent--in this case, myelin-reactive T cells--that have been selected and expanded from each MS donor and then re-injected after irradiation to induce protective immunity. This anti-T-cell immunity consistently results in selective deletion or regulation of the targeted pathogenic T cells in vivo. Longitudinal studies have established that TCV is safe and often results in a reduced relapse rate and clinical stability or improvement, at least temporarily, in the majority of treated MS patients. These results lend direct support to the involvement of inflammatory myelin-reactive T cells in the MS disease process. However, these hopeful trends reported in a number of pilot trials await validation in larger proof-of-principle trials that are now in progress.

Immune responses to polyclonal T-cell vaccination in patients with progressive multiple sclerosis

“…TCR immunogenicity provides the rationale for using T-cell vaccination to induce anti-idiotypic immune responses with the purpose of down-regulating functionality of idiotype-bearing, self-reactive T-cells. The disappearance of T-cell clones used in the vaccination procedure has been one of the most consistent findings of the various studies (Vandenbark & Abulafia-Lapid 2008).…”

“…Of great importance is that the variable TCR regions are finally formed in the post-natal period and, therefore, no innate immune tolerance to them exists in the adult body. Moreover, idiotypic TCR determinants are firmly established to be immunogenic and capable of eliciting an anti-idiotype immune responses, which are implicated in down-regulation of autoimmune processes (Seledtsov et al 2010;Vandenbark & Abulafia-Lapid 2008).…”

“…Therapies revolve around five drug classes: nonsteroidal anti-inflammatory drugs, anti-malarials, steroids, immunosuppressive drugs, and biological therapies. However, none of these disease-modifying drugs is a "cure", and each displays the potential for serious adverse events (Huang et al 2014;Vandenbark & Abulafia-Lapid, 2008). In particular, all of them suppress not only harmful autoimmune, but also useful protective immune responses.…”

The future of multiple sclerosis treatments

“…A number of animal studies and human clinical trials of T-cell vaccination in MS have been conducted and reviewed [166,167]. TCV include an attenuation step to preventing the encephalitogenicity of myelin-reactive T cells and is safe.…”

“…TCV include an attenuation step to preventing the encephalitogenicity of myelin-reactive T cells and is safe. Two phase II, placebo-controlled clinical trials of TCV in MS were reported [167,168]. Fox et al showed that treatment with myelin-reactive T-cells against up to six peptides of MBP, MOG and PLP was safe in 100 RRMS and CIS patients, of which 44% were previously treated with DMTs [168].…”