Treatment and prevention of experimental autoimmune neuritis with superagonistic CD28-specific monoclonal antibodies

Costimulation and Autoimmune Diabetes in BB Rats

“…Similarly, we now show that anti-CD28 mAbs prevent diabetes in BBDP rats when treatment is started before disease initiation. The agonistic anti-CD28 mAb (JJ316) prevents experimental autoimmune neuritis (55), and is hypothesized to mediate these activities by inducing Tregs (40). Our data document that JJ316 anti-CD28 mAb increases CD4 + CD25 + T-cell numbers in lymphopenic BBDP rats.…”

Selective expansion of memory CD4+ T cells by mitogenic human CD28 generates inflammatory cytokines and regulatory T cells

“…The clinical use of It now appears that mitogenic CD28 mAb induce high levels of inflammatory cytokines both in vivo and in vitro, challenging the clinical efficacy of these antibodies. The groups of Hünig and Hanke reported selective expansion of regulatory T cells by mitogenic rat or human CD28 [6][7][8][9][10][11][12][13], yet the mitogenic antihuman CD28 caused a cytokine storm in the Phase I in vivo trial [15,16]. Our study provides a plausible explanation for this contradiction; (i) stimulation through mitogenic CD28 activates pathogenic effector T cells as well as protective regulatory T cells.…”

“…The groups of Hünig and Hanke [6][7][8][9][10][11][12][13] extensively characterized the mitogenic anti-rat CD28 mAb JJ316, which preferentially expanded regulatory T cells (Treg) and induced anti-inflammatory cytokines in vitro and in vivo with therapeutic abilities in vivo. In particular, JJ316 prevented EAE and adjuvant arthritis in rats [6,10].…”

REVIEW ARTICLE: Regulatory T Cells and Their Role in Pregnancy

“…123 Application of substances that specifically expand Treg, like the CD28 super agonist, seemed to be a very promising therapy. [124][125][126][127][128][129] However, the initial hope to use therapies that expand Treg was hampered by the data provided by Suntharalingam and colleagues 130 who reported that the application of the humanized monoclonal antibody to CD28, TGN1412, which should have expanded the Treg population, to young healthy volunteers ended in a medical disaster. The patients first showed a systemic inflammatory response accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension and then became critically ill, with lung injury, renal failure, and disseminated intravascular coagulation.…”