Thioredoxin 1 (Trx1) is a redox sensitive protein that plays a major role in regulating cellular oxidative stress. Extracellular Trx1 has been shown to regulate immune cell biology. Oblique has identified several potent aTRX mAbs that bind and neutralize Trx1 activity. These antibodies are being evaluated for immune modulation and anti-tumor activity in syngeneic and humanized tumor models.
Plasma levels of Trx1 is elevated in patients with lung, breast, colorectal, pancreatic, hepatocellular, gastric, myeloma, non-Hodgkin lymphoma and acute lymphatic lymphocytic leukemia. Trx1 is believed to be a survival factor and chemoattractant to Tregs in tumor microenvironment (TME) resulting in inhibition of cytotoxic T cells and NK cells. By neutralizing Trx1 in TME, an aTRX mAb is hypothesized to reduce Treg and other suppressive cells and activate T effector cells, thereby resulting in anti-tumor immune response and reduction in formation of pre-metastatic niche.
Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive subgroup characterized by the lack of over-expression of the human epidermal growth factor 2 (HER2) in addition to the absence of progesterone and estrogen receptors. Unlike hormone positive and HER2 positive breast cancers, there are no effective targeted therapies for TNBC. According to WHO estimate, over two million people were diagnosed with breast cancer in 2020 with ~700,000 succumbing to the disease worldwide: of them, around 10-20% would historically be TNBC.
TNBC is highly heterogeneous and often recur after initial response to standard of care chemotherapies. Recurrent and metastatic TNBC has very few effective treatment options. In general, the prognosis of TNBC is very poor and the median survival of patients with metastatic disease is less than 12 months.