On Sept. 12, at the American Association for Cancer Research (AACR)’s 11th Biennial Ovarian Cancer Research Symposium in Seattle, Siamab Therapeutics declared that its new ST1 antibody drug conjugates (ADCs) have the ability to target chemotherapy-resistant ovarian cancer cells, showing strong efficacy in ovarian cancer models.
“We have developed multiple anti-glycan antibodies and ADCs with unprecedented cancer specificity and efficacy in animal models. These findings hold promise for developing new cancer therapeutics for ovarian cancer patients with disease recurrence who have limited treatment options,” Jeff Behrens, president and CEO of Siamab Therapeutics, said in a press release.
Siamab’s focus is on optimizing rapid discovery and development of therapeutic antibodies that bind with unsurpassed accuracy and rate to a specific type of carbohydrate-based antigens (molecules that induce immune responses) on the surface of cancer cells called tumor-associated carbohydrate antigens (TACAs). TACAs’ importance for cancer research lies on four separate issues: they are cancer specific, associated with chemoresistance, associated with metastasis, and able to act in a locally immunosuppressive way around solid tumors.
ST1-ADCs, Siamab’s flagship project, is designed to act as a missile targeting Sialyl-Tn (STn), a tumor-specific antigen expressed by multiple solid tumors like pancreatic, prostate and colon cancers, in addition to ovarian cancer. Also, STn defines a population of cells that display a cancer stem cell (CSC) phenotype. Additionally, the STn-related approach garners additional accolades when considering the antigen shows little normal tissue expression.
The preclinical analysis, summarized and demonstrated in a poster at the event, seems to support Behrens’s expectations for ST1-ADCs. “The preclinical results are exciting and show the potential of our antibody approach to target chemo-resistant tumors in ovarian cancer,” he said.
The research, which was funded by a National Cancer Institute SBIR Phase I contract, concludes in preliminary results that following the cytotoxic effects of chemotherapy, STn-positive cancer cells are significantly enriched, further supporting their cancer stem cell and chemo-resistant phenotype.
“We know chemo-resistant cancer cells play a central role in disease recurrence and are particularly challenging to target,” said Bo Rueda, PhD, director of the Vincent Center for Reproductive Biology in the Department of Obstetrics and Gynecology at Massachusetts General Hospital, and collaborator in this endeavor.
Rueda, who also explores the association between TACAs and chemo-resistant cancer cells that encompass a cancer stem cell phenotype, added: “Siamab’s ADCs targeted STn-positive cells, demarking a chemo-resistant population, and were effective in shrinking ovarian tumors in animal models. I look forward to continuing to work closely with Siamab as they move this program toward clinical development.”