CD28 is a cell surface glycoprotein receptor that is expressed primarily on activated T cells. It is a member of the immunoglobulin superfamily, also known as T44 or Tp44, which provides critical co-stimulatory signals. The CD28 gene consists of four exons encoding a 220 amino acid protein expressed as a 44 kDa glycosylated, disulfide-linked homodimer on the cell surface. CD28 is essential for the proliferation and effector functions of conventional T cells and also promotes the anti-inflammatory functions of regulatory T (Treg) cells, preventing spontaneous autoimmunity by promoting Treg function.T cell immunity requires a dual signaling system for activation, in which CD28/B7 molecule-mediated continuator signaling plays an essential role.

Reltecimod (AB-103) is a CD28 (TP44) antagonist.

From: Manzoor Ahmad Mir, et al. ISBN: 978-1-62948-213-2

Reltecimod, also known as AB-103, is a T-cell specific surface glycoprotein CD28 (TP44) antagonist. It modulates the inflammatory response by targeting and attenuating the critical CD28/B7-2 co-stimulatory pathway without inhibiting it. Also, Reltecimod shows good resistance to different bacterial infections, bacterial exotoxin and endotoxins, and ionizing radiation. Reltecimod also plays a role in necrotizing soft tissue infections (NSTIs).

In several in vivo experiments, for instance, Reltecimod (1.25 or 5 mg/kg; i.v.) increases the survival rate of female BALB/c mice infected with E. coli 018:K1 to induce acute bacterial peritonitis. It results in 100% survival at a single dosage of 5 mg/kg, and 70% survival at 4 dosages (at 1, 12, 24 and 36 h post-infection) of 1.25 mg/kg, at day 6. Besides, in BALB/c mice NSTI model infected with Streptococcus pyogenes by thigh i.m. administration, Reltecimod (2.5 or 5 mg/kg; i.v.) results in 65% survival at single dosage of 2.5 mg/kg, 30% survival at two dosages (1 and 12 h post-infection) of 2.5 mg/kg, and 90% survival at single dosage (1 h post-infection) of 5 mg/kg, at day 8. Moreover, Reltecimod (1.25, 2.5, or 5 mg/kg; i.v.) can increase day 7 survival by up to 100% in the BALB/c mice cecal ligation and puncture (CLP) model.

In conclusion, Reltecimod is a T cell-specific surface glycoprotein CD28 (TP44) antagonist with some resistance to bacterial infections.

References:

[1] Esensten JH, et al.  Immunity. 2016 May 17;44(5):973-88.
[2] Edgar, R., et al.Int J Pept Res Ther 26, 1669–1683 (2020).