Please input keywords

YH006 is a fully human CTLA-4 x OX40 IgG1 bispecific antibody produced by RenLite mice of fully human antibodies with a common light chain and very close to monoclonal antibody in the structural style. YH006 reduces the CTLA-4 toxicity and treat tumors mainly by more specifically removing tumor-infiltrating Treg cells.

from clipboard

The structure of YH006

Preclinical studies have shown the following findings:
1. CTLA-4 and OX40 are co-expressed and highly expressed in tumor-infiltrating Tregs. The dual targets enable more specific identification of tumor-infiltrating Tregs. YH006 has stronger in vivo anti-tumor activity.

from clipboard

Figure 1. In the MC38 syngeneic mouse tumor model, YH006 better inhibited tumor growth than ipilimumab analogs and Fc-enhanced parental IgG1 monoclonal antibody

2. YH006 addresses the double-antibody mismatch with a common light chain and provides good stability and druggability.

from clipboard

Figure 2. The fully human bispecific antibody YH006 with high purity and good stability is obtained in one step

CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4), also known as CD152, plays an important regulatory role in the activation of T cells. CTLA-4 is expressed on the surface of regulatory T cells (Tregs), and when bound to B7-1 (CD80) and B7-2 (CD86) on the surface of antigen-presenting cells (APCs), competitively inhibits the binding of B7 to CD28 on the surface of effector T cells, thereby inhibiting the activation of T cells. Therefore, inhibition of CTLA-4 by inhibitory antibodies can block this mechanism, thereby enhancing T cell activity.

Currently, the marketed antibody drugs targeting CTLA-4 include CTLA-4 mAb ipilimumab (Yervoy) from BMS and PD-1 x CTLA-4 bispecific antibody cadonilimab (trade name: Kaitanni; AK104) from Akeso.

OX40 is a type I transmembrane glycoprotein, a member of the tumor necrosis factor receptor superfamily (TNFRSF), and an important costimulator of T cell response. OX40 is not expressed on naïve T cells, but is transiently expressed on CD4+ and CD8+ T cells after TCR engagement, enhancing the TCR signaling, promoting the proliferation and survival, as well as the release of effector cytokines, and preventing T-cell tolerance. In addition, activation of OX40 inhibits the production and secretion of inhibitory cytokines including IL-10 and TGF-b by Treg cells. Moreover, OX40 plays an important role in the formation of memory T cells.

There are currently no marketed OX40 drugs.