The company specializes in liver-related services and has evaluated test substances in over 15 MOA categories as well as over 270 target molecules using the STAM™ mouse.

The STAM™-HCC/IO⁺ mouse is a model that allows stable evaluation of the growth of multiple target lesions originating from the liver over a certain period. Furthermore, it can be used for testing molecular target drugs and immune checkpoint inhibitors, and for other therapeutic targets while performing stable drug efficacy evaluations. The market for immunotherapy drugs based on immuno-oncology is increasing every year, and a variety of tumor immunotherapy drugs such as stromal modifying agents, adaptive cell therapy, tumor targeting antibodies, immunogenic cell death inducers, metabolic inhibitors, and immune effector cell modulators are being developed. As the prevalence of liver cancer increases, it is anticipated that SMC Laboratories' STAM™-HCC/IO⁺ mouse will greatly contribute to the development of therapeutic drugs for liver cancer in the future.

Liver cancer is the fourth most common type of cancer in the world (Huang DQ et al, Nature Reviews Gastroenterology & Hepatology, 18, 223-238, 2021). The proportion of MASH/NASH patterns with non-virus-related cancer is also increasing annually. In addition to molecular target drugs such as lenvatinib and sorafenib, immune checkpoint inhibitors (ICIs) such as atezolizumab + bevacizumab, nivolumab, and pembrolizumab have also recently been used in clinical practice as therapeutic drugs for liver cancer. Therefore, future developments are highly anticipated. (Chen C et al, frontiers in Immunology, 14, 1133308, 2023). However, the response rate of ICIs for liver cancer is still low, ranging from 0-14%, compared to other types of cancer (e.g., melanoma response rate; 35-70%), thus there is a great demand for the development of new treatments. (Tan S et al, JACC: CardioOncology, 4, 579-597, 2022, Valero C et al, JAMA Oncology, 7, 1245-1246, 2021). Due to this information, along with recent revelations int the field of tumor immunology, SMC Laboratories has successfully leveraged the characteristics of its STAM™-HCC/IO⁺ mouse, which enables the provision of non-clinical pharmacological services for new liver cancer therapeutics, including ICIs.

Through the company's research, it has become apparent that the STAM™-HCC/IO⁺ mouse model has a high tumor mutation burden with the following features:

• Tumor-infiltrating T cells (TILs), CD8⁺ cytotoxic T cells (CTLs)
• ICI monotherapy and/or combination therapy
• Tumor microenvironmental components
• Changes from baseline [sum of the longest diameters of target lesions]

These characteristics are extremely useful in evaluating treatments based on tumor immune control in non-clinical studies, and the STAM™-HCC/IO⁺ mouse, which has all of these features, is currently the most suitable non-clinical liver cancer mouse model for tumor immunology research (Shalapour S et al, Nature, 551, 340-345, 2017, Dow M et al, PNAS, 115: E9879-E9888, 2018). It is possible to evaluate the anti-tumor effects of ICIs not only in monotherapy studies but also in combination studies. This can be accomplished by using anti-PD-L1 antibody as a control, and directly comparing results.