Anti-Tox Monoclonal antibody, clone UYSY20 [PE]

A transcription factor with DNA-binding function, TOX (thymocyte selection-associated high mobility group box protein) is a member of the high mobility group protein superfamily. TOX exists on chromosomes, with four gene subfamilies. They are highly conserved in animal species with unique expression patterns and functions.

TOX1 sits in the q12.1 slot on human chromosome 8 and encodes only one transcript that encodes a protein with 526 amino acids. It's expressed in thymus, spleen, bone marrow, kidneys and pancreas among other human tissues. Tox helps form CD4⁺ T cells, natural killer cells and naturally occurring lymphoid cells. TOX2 is found on the q13.12 region of human chromosome 20 and has four transcripts, resulting in a protein of 506 amino acids. The specific functions of TOX2 in the human body are not yet fully understood; however, it has been reported that TOX2 can alter chromatin and influence its function, thereby promoting the development of T follicular helper (TFH) cells and NK cells. TOX3 is situated on the q12.1 region of human chromosome 16 and has two transcripts that encode a protein with 576 amino acids. TOX3 is considered an important protective factor for neurons. TOX4 is found on the q11.2 area of human chromosome 14 and has two transcripts that make a protein of 621 amino acids. It's mostly involved in biological regulation of cell cycle, proliferation, apoptosis and embryonic stem cell development.

Figure 1. Schematic diagram of the TOX gene structure and location
(Source: Liang C, et al. 2021)

In recent years, TOX has been identified as a key transcription factor regulating CD8⁺ T cell exhaustion. T cells undergo gene-expression and epigenetic change, such as overexpressed TOX, under chronic infection or chronic antigen stimulation by tumor antigens. Combined with these, we find heightened expression of immune checkpoint molecules such as PD-1, Tim-3 and TIGIT, changes in cell metabolism and a gradual loss of effector T-cell function mainly defined by impaired proliferation, diminished survival and cytokine production. This phenomenon in T cells is referred to as T cell exhaustion. In one study, researchers found TOX as an upstream signalling molecule for immune checkpoints, and TOX levels were strongly correlated with immunosuppressive molecules (PD-1, PD-L1, CTLA-4). Elevated TOX expression in CD8⁺ T cells is closely associated with poor efficacy of anti-PD-1 therapies. Furthermore, TOX expression appears to be unique to the exhausted phenotype and has not been detected in naive T cells, memory cells, or effector cell subsets. It is widely accepted that TOX is a prominent feature of terminally exhausted T cells and serves as one of the indicators defining the exhausted T cell subset alongside PD-1, CD39, transcription factor 1 (TCF-1), Ly108, and CD69, thereby enriching the diversity of exhausted T cell subsets

Anti-thymocyte selection-associated high mobility group box protein monoclonal antibody