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The sialylated version of the carbohydrate Tn antigen is rarely expressed in normal adult human tissues, but it frequently occurs in human solid cancers including breast, ovarian, bladder, cervical, colon, and lung cancer. This demonstrating high tumor specificity and broad tumor expression. In addition, the presence of STn in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. [1] [2]

Preclinical data shows that Siamab Therapeutics novel anti-Sialyl-Tn (STn) antibodies and antibody-drug conjugates (ADCs) targeting myeloid-derived suppressor cells (MDSCs) may offers a potential targeting mechanism for treatment of solid tumors.

The data was presented during the Cambridge Healthtech Institute’s Inaugural Targeting Tumor Myeloid Cells Conference, held September 27-28, 2017 in Boston.


“…these results further our understanding of myeloid-derived suppressor cells (MDSCs) and suggest the potential for a functional role of STn… It highlights the possibility to directly impact MDSC function with immuno-therapeutic applications…”


Researchers at Siamab Therapeutics generated anti-STn mAbs having no cross-reactivity to the asialylated form of STn (Tn) or other glycan antigens [3]

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Their data show that STn, a tumor-associated carbohydrate antigen (TACA), is expressed not only on tumor cells, but also on tumor infiltrating MDSCs, providing a potential new therapeutic target.

MDSCs are major regulators of immune responses in cancer and other pathological conditions and play a critical role in the tumor microenvironment by suppressing T-cell immunity (they are functionally defined by their capacity to suppress T cell immunity) making them of great interest for immuno-oncology applications.

During the oral and poster presentations, researchers from Siamab reported data from primary human cancer samples as well as from two in vivo murine studies. In the studies, the researchers used monoclonal antibodies (mAbs) to quantify the expression of STn across patient tumors, and for the first time demonstrated the expression of STn on subsets of tumor infiltrating immune cells, specifically MDSCs. [3]

The findings showed that STn provides a uniquely glycan-specific and potent targeting mechanism for the treatment of solid tumors using Siamab’s anti-STn antibody drug conjugates. Additionally, the findings showed a correlation between MDSC STn expression and tumor STn expression using murine xenograft models of tumors with controlled STn expression.

The epitope targeted by these mAbs is the STn glycan itself, not a particular glycopeptide or carrier protein, which offers the broadest potential to bind to multiple STn-glycosylated proteins on cell surfaces. Researchers at Siamab Therapeutics have used these mAbs to quantify specifically the expression of tumor STn across a set of patient samples and for the first time demonstrated the expression of STn on subsets of infiltrating myeloid derived suppressor cells (MDSCs).

The researchers further evaluated the correlation between MDSC STn expression and tumor STn expression using murine xenograft models of tumors with controlled STn expression. Using anti-STn antibody-drug conjugates (ADCs), they were able to demonstrated that STn provides a uniquely glycan-specific and potent targeting mechanism for treatment of solid tumors.

Based on their pre-clinical data, researchers conclude that STn expression on MDSCs may offers the potential to go beyond tumor targeting with an anti-STn therapeutic to also directly target and deplete immune-suppressive MDSCs, fostering immune re-engagement and possibly better patient outcomes. The emerging understanding of glycans in immunology and specifically MDSC biology suggests the potential for a functional role of STn as well and provides a compelling opportunity to directly impact MDSC function with immuno-therapeutic applications.

“These preclinical findings are important as they reveal that STn expression on MDSCs offers the possibility to go beyond tumor targeting with an anti-STn antibody therapeutic to directly target and deplete immune suppressive MDSCs and re-engage the immune system,” noted Jeff Behrens, president and chief executive officer of Siamab.

“We are encouraged by these results which further our understanding of MDSCs and suggest the potential for a functional role of STn, highlighting the possibility to directly impact MDSC function with immuno-therapeutic applications. We look forward to further evaluating our anti-STn antibody therapeutics against STn expressing solid tumors and MDSCs,” Behrens added.

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