STCube Presents 'New Biomarker for Colorectal Cancer' at AACR

STCube identified BTN1A1 as a key regulatory factor that increases cancer malignancy and induces resistance to immune checkpoint inhibitors, and based on this, suggested the broad expansion potential of anti-BTN1A1 immunotherapy.

On the 26th, STCube announced that it will present two abstracts at the ‘2025 American Association for Cancer Research Annual Meeting (AACR 2025)’ to be held in Chicago, USA, from April 25 to 30. The research results focus on the role of BTN1A1 as a reliable biomarker for colon cancer and the BTN1A1-YAP1 dual-target immunotherapy strategy.

The first presentation topic is “BTN1A1 and YAP1 Expression as Biomarkers in Colon Cancer: Phase 1b Trial Results of hSTC810.” It will be a focused poster presentation on the expression patterns of BTN1A1 and YAP1 and their potential as novel biomarkers observed in the Phase 1b investigator-initiated clinical trial of colon cancer, conducted to confirm the efficacy of the combination therapy of Nelmastovat and capecitabine.

The second presentation topic is “BTN1A1 and YAP1 crosstalk: A key mechanism in tumor immune evasion and therapeutic targeting.” This study elucidates the impact of the interaction between BTN1A1 and YAP1 on cancer cell growth and immune regulation, and presents the possibility of developing next-generation immuno-oncology drugs that dual-target BTN1A1-YAP1.

BTN1A1 is an immune checkpoint protein that suppresses immune function in both immune cells and cancer cells. YAP1 is a major factor that promotes cancer cell proliferation and increases resistance to anticancer drugs, observed in various cancers including colon and lung cancer. Previous studies have reported that suppressing YAP1 overexpression inhibits cancer cell growth and increases sensitivity to anticancer drugs.

STCube’s research team confirmed that BTN1A1 and YAP1 interact and co-localize in various solid tumors, and that YAP1 induces BTN1A1 expression, thereby activating immune evasion functions. BTN1A1 not only regulates T cell immune function but also plays an important role in the expression and activation of YAP1. STCube verified therapeutic effects through 3D spheroid experiments using colon cancer cell lines (combination therapy of Nelmastovat and TAS-102) and lung cancer cell lines (combination therapy of Nelmastovat and docetaxel).

Seunghan Yoo, Chief Scientific Officer (CSO) of STCube, said, “This is a very important research achievement demonstrating that Nelmastovat, which has extremely limited toxicity to normal tissues, can effectively control BTN1A1 to overcome not only cancer immune evasion but also resistance to anticancer drugs.” He added, “BTN1A1 is an innovative new target and biomarker for immuno-oncology therapy, and its potential has already been proven in actual clinical cases of colon cancer.”

He continued, “The anticancer effect of Nelmastovat in BTN1A1-positive patients has been confirmed in multiple clinical trials with high objective response rates (ORR) and sustained progression-free survival (PFS). Adding Nelmastovat to existing standard treatments such as chemotherapy can be expected to provide safer and more fundamental therapeutic effects.” He explained, “This is because Nelmastovat, which targets dormant or slowly growing seed cancer cells, works synergistically with other therapies targeting rapidly growing cancer cells to produce a strong combination treatment effect.”

Furthermore, he stated, “Therefore, these research results provide very important academic and clinical evidence suggesting the potential success of BTN1A1 biomarker-based clinical trials. The currently planned colon cancer clinical trial will be conducted only on BTN1A1-positive patients, so more effective treatment outcomes are expected.”

On the 20th, STCube received approval from the Ministry of Food and Drug Safety for the Phase 1b/2 clinical trial application (IND) of the combination therapy of Nelmastovat, TAS-102, and bevacizumab for the treatment of metastatic/recurrent colon cancer.

The TAS-102 and bevacizumab combination therapy is known as the most effective global standard treatment among third-line or later metastatic colon cancer standard therapies. STCube plans to confirm dose-limiting toxicity (DLT) in Phase 1b and then verify efficacy in BTN1A1-positive patients in Phase 2.