Press Release

Development of a Fully Automated Measurement Method for Soluble Immune Checkpoint Molecules (sPD-1, sPD-L1 and sCTLA-4)

Sysmex Corporation (HQ: Kobe, Japan; Chairman & CEO: Hisashi Ietsugu) and Kyoto University (Sakyo-ku, Kyoto, Japan; President: Juichi Yamagiwa) announce the development of a fully automated measurement method for soluble immune checkpoint molecules (sPD-1, sPD-L1 and sCTLA-4) through joint R&D conducted since 2013 by Sysmex and Tasuku Honjo, a distinguished professor at the Kyoto University Institute for Advanced Studies. The two parties will proactively conduct clinical research using this measurement method to create new diagnostic technologies for cancer and immune disease.

“Immune checkpoint molecule” is a general term for the multiple molecules (proteins) that help maintain the body’s immune homeostasis1 by activating or suppressing the immune function. Immune checkpoint molecules are known to be involved in autoimmune diseases2 and cancer immune escape.3
Recent years have seen the establishment of cancer immunotherapy as a new cancer treatment method. In this method, antibodies that combine with immune checkpoint molecules are administered to cancer patients and that inhibit the immunosuppressive function to reactivate immunity. As this approach is recognized to be effective for various types of cancer, many pharmaceutical companies are developing therapeutic drugs. In 2018, Tasuku Honjo, distinguished professor at the Kyoto University Institute for Advanced Studies, and Dr. James P. Allison of the MD Anderson Cancer Center at the University of Texas received the Nobel Prize in Physiology or Medicine by proposing the use of immune checkpoint molecules in cancer treatment.
Cancer immunotherapy has been shown to produce strong therapeutic results in patients who have not seen therapeutic results with conventional anticancer drugs. However, the advance selection of patients likely to experience drug efficacy has been difficult. Also, various immune-related adverse events can occur, so a search had been underway for a biomarker to predict therapeutic results and the presence of adverse events.
When studying the body’s immune function to connect diagnosis and prognostic testing for cancer and autoimmune diseases, Professor Honjo noted that some of the immune checkpoint molecules (PD-1, PD-L1 and CTLA-4) normally present on the cell surface membrane were present in the blood as soluble immune checkpoint molecules (sPD-1, sPD-L1 and sCTLA-4). Many researchers had sought to verify a relationship between cancer and immune disease and soluble immune checkpoint molecules present in the blood, but accurately measuring such molecules had been difficult because of the small quantities present. Since 2013, Professor Honjo and Sysmex have been conducting joint research to create a highly sensitive method for measuring soluble immune checkpoint molecules in the blood that placed a small burden on patients and allowed the immune status to be determined simply.

The two parties have developed fully automated method for measuring soluble immune checkpoint molecules that uses the HI-1000, an automated, highly sensitive immunoassay system for research applications. This measurement method uses chemiluminescence enzyme immunoassay (CLEIA) as its measurement principle. Fully automating the measurement method allows the measurement of soluble immune checkpoint molecules to be conducted in 17 minutes (100 tests/hour) and achieves high levels of sensitivity and reproducibility.4

In September 2019, Sysmex began providing assay services for research using this measurement method.

As the measurement method can be used in cancer immunotherapy and as a new method for diagnosing autoimmune diseases, and has the potential to help realize personalized medicine, the two parties will promote R&D with a view toward commercialization, contributing to advances in healthcare.



Overview of the Measurement Method

Parameters sPD-1 sPD-L1 sCTLA-4
Measurement principle CLEIA (automatic)
Detection sensitivity
3.9 6.8 0.4
Dynamic Range
10.0 - 5000.0 25.0 - 5000.0 1.0 - 5000.0

Website of Assay Services for Research


  1. Immune homeostasis:
    Refers to the function of maintaining a steady level of immunity by enhancing immunity to protect the body from external pathogens, while suppressing it to prevent excessive immune enhancement. 
  2. Autoimmune diseases:
    Immunity normally plays the role of protecting the body from incursion by foreign matter. Autoimmune diseases occurs when these immune cells mistake the body’s cells and tissues as foreign matter and attack them.
Autoimmune diseases include connective tissue disease, thyroid disease, myasthenia gravis and type 1 diabetes, and so on.
  3. Cancer immune escape:
    Cancer cells are known to use immune checkpoint molecules’ immunity suppressive function to avoid attack by the immune system.
  4. Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma
Scientific Reports 2019; vol. 9, 10144
  5. pg (picogram):
    1 pg = 1 one-trillionth of a gram

About Sysmex Corporation
In line with its mission of “shaping the advancement of healthcare,” which is defined in the “Sysmex Way,” the corporate philosophy of the Sysmex Group, Sysmex works to contribute to the development of healthcare and the healthy lives of people. Sysmex provides integrated R&D, manufacturing, sales, service and support for the instruments, reagents and software needed for in vitro diagnostics of blood, urine and other samples. Sysmex provides products to healthcare institutions in more than 190 countries and regions.
In recent years, Sysmex’s business has been expanding into the life science domain. The company is using proprietary technologies to create new testing and diagnostic value in the aim of realizing healthcare that is optimized for individual patients, reducing the burden on patients and helping to increase their quality of life. To learn more about Sysmex Corporation, visit

About Kyoto University
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information please see:
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