Trivalent T Cell Receptor Peptide Vaccine for Treatment of Multiple Sclerosis Targets Predominant V Genes Widely Implicated in Autoimmune Diseases and Allergy

Vandenbark, Arthur A.; Culbertson, Nicole

doi:10.1007/978-0-387-36003-4_16

Cited by 1 publication

(2 citation statements)

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“…Our meta-analysis of $1000 AV and BV genes from neuroantigen-specific T cells from $ 200 MS subjects revealed BV5S2, BV6S5 and BV13S1 as excellent candidate BV gene targets. 10 On the basis of successful therapeutic vaccination in the EAE model using complementarity determining region (CDR) 2 peptides, we developed a trivalent TCR vaccine using these three CDR2 peptides emulsified in incomplete Freund's adjuvant (IFA). 11 Several blinded studies using both single and multiple TCR peptides demonstrated that TCR vaccination could induce high frequencies of TCRspecific T cells concomitant with suggestions of clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

“…Development of TCR peptide vaccination as a treatment for MS first required the identification of target TCR BV genes and the creation of a vaccine capable of reliably boosting TCR reactive T cells. Our meta‐analysis of ∼1000 AV and BV genes from neuroantigen‐specific T cells from ∼ 200 MS subjects revealed BV5S2 , BV6S5 and BV13S1 as excellent candidate BV gene targets 10 . On the basis of successful therapeutic vaccination in the EAE model using complementarity determining region (CDR) 2 peptides, we developed a trivalent TCR vaccine using these three CDR2 peptides emulsified in incomplete Freund's adjuvant (IFA) 11 .…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic vaccination with a trivalent T‐cell receptor (TCR) peptide vaccine restores deficient FoxP3 expression and TCR recognition in subjects with multiple sclerosis

et al. 2007

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Summary Therapeutic vaccination using T‐cell receptor (TCR) peptides from V genes commonly expressed by potentially pathogenic T cells remains an approach of interest for treatment of multiple sclerosis (MS) and other autoimmune diseases. We developed a trivalent TCR vaccine containing complementarity determining region (CDR) 2 peptides from BV5S2, BV6S5 and BV13S1 emulsified in incomplete Freund's adjuvant that reliably induced high frequencies of TCR‐specific T cells. To evaluate induction of regulatory T‐cell subtypes, immunological and clinical parameters were followed in 23 treatment‐naïve subjects with relapsing‐remitting or progressive MS who received 12 monthly injections of the trivalent peptide vaccine over 1 year in an open‐label study design. Prior to vaccination, subjects had reduced expression of forkhead box (Fox) P3 message and protein, and reduced recognition of the expressed TCR repertoire by TCR‐reactive cells compared with healthy control donors. After three or four injections, most vaccinated MS subjects developed high frequencies of circulating interleukin (IL)‐10‐secreting T cells specific for the injected TCR peptides and significantly enhanced expression of FoxP3 by regulatory T cells present in both ‘native’ CD4+ CD25+ and ‘inducible’ CD4+ CD25− peripheral blood mononuclear cells (PBMC). At the end of the trial, PBMC from vaccinated MS subjects retained or further increased FoxP3 expression levels, exhibited significantly enhanced recognition of the TCR V gene repertoire apparently generated by perturbation of the TCR network, and significantly suppressed neuroantigen but not recall antigen responses. These findings demonstrate that therapeutic vaccination using only three commonly expressed BV gene determinants can induce an expanded immunoregulatory network in vivo that may optimally control complex autoreactive responses that characterize the inflammatory phase of MS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%