ATHEROSCLEROSIS
Working in collaboration with LJI Professor Klaus Ley, the Sette Lab aims to help develop vaccines that target inflammatory factors as a means to reduce atherosclerotic plaque formation. The researchers have identified several peptides suitable for vaccinating humans. The aim is to test those in mice engineered to harbor a humanized immune system. Their current goal is to enter phase I clinical trials. If successful, this achievement would constitute the worlds’ first vaccine for heart disease.
Selected References
Kimura T, Tse K, McArdle S, Gerhardt T, Miller J, Mikulski Z, Sidney J, Sette A, Wolf D, Ley K. Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells. Am J Physiol Heart Circ Physiol. 2017 Apr 1;312(4):H781-H790. doi: 10.1152/ajpheart.00798.2016. Epub 2017 Jan 13. PMID: 28087520; PMCID: PMC5407161.
Kimura T, Kobiyama K, Winkels H, Tse K, Miller J, Vassallo M, Wolf D, Ryden C, Orecchioni M, Dileepan T, Jenkins MK, James EA, Kwok WW, Hanna DB, Kaplan RC, Strickler HD, Durkin HG, Kassaye SG, Karim R, Tien PC, Landay AL, Gange SJ, Sidney J, Sette A, Ley K. Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B. Circulation. 2018 Sep 11;138(11):1130-1143. doi: 10.1161/CIRCULATIONAHA.117.031420. PMID: 29588316; PMCID: PMC6160361.
Wolf D, Gerhardt T, Winkels H, Michel NA, Pramod AB, Ghosheh Y, Brunel S, Buscher K, Miller J, McArdle S, Baas L, Kobiyama K, Vassallo M, Ehinger E, Dileepan T, Ali A, Schell M, Mikulski Z, Sidler D, Kimura T, Sheng X, Horstmann H, Hansen S, Mitre LS, Stachon P, Hilgendorf I, Gaddis DE, Hedrick C, Benedict CA, Peters B, Zirlik A, Sette A, Ley K. Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B100-Reactive CD4+ T-Regulatory Cells. Circulation. 2020 Sep 29;142(13):1279-1293. doi: 10.1161/CIRCULATIONAHA.119.042863. Epub 2020 Jul 24. PMID: 32703007; PMCID: PMC7515473.