Accurately Killing Tumor Antigens: Tianfu Life Science Park Enterprise Develops

In recent years, entrepreneurs in the pharmaceutical industry have been focusing on researching and developing innovative drugs in China, with anti-tumor drugs being a popular direction for many. "If you want to make an innovative anti-tumor drug, the first step is to develop your own anti-tumor antibodies. In the past, China was far behind in the field of antibody drug discovery, so I chose to start a business here and use the 'hundred-billion-level' antibody library I developed to create innovative anti-tumor antibodies," said Liu Jianghai, who founded Chengdu Shengshi Junlian Biotechnology Co., Ltd (ABLINK) in Chengdu Tianfu Life Science Park in 2016.

Why needs antibody library for developing innovative drugs?

“Tumors are very complex but also very unique. They often express mutated proteins or overexpress proteins associated with tumor growth and proliferation, which we call tumor antigens or drug targets. That's why you often hear the term targeted therapy.” Traditional cancer treatment said by Liu Jianghai relies more on the use of small molecule chemical drugs, which we commonly refer to as chemotherapy. These drugs often kill healthy cells along with cancer cells, causing side effects such as hair loss, reduced white blood cell counts, and overall body pain. “However, the killing effect of antibody drugs is very precise. They only kill tumor cells without harming normal cells, so generally, antibody drugs have low toxicity.” Liu Jianghai said.

In 2013, a friend's mother of Liu Jianghai was diagnosed with breast cancer. "At that time, they didn't understand targeted drugs and opted for conservative treatment. By then, my friend's mother was unable to get out of bed." Later on, the friend asked Liu Jianghai if the antibodies or targeted drugs he was researching could possibly treat breast cancer. "I suggested that she have gene diagnosis done to see which target or antigen caused this tumor. It turned out one of the targets was Her2, and later on, my friend's mother used trastuzumab (an antibody drug that can target Her2). Three months later, her tumor visibly shrunk, and she began to get out of bed, exercise, cook, and live a normal life. She persisted until she passed away in 2018 when the tumor relapsed."

In recent years, both the government and enterprises have realized the importance of developing innovative drugs. Many entrepreneurs have chosen to develop novel tumor-targeted antibodies as their entrepreneurial choice. However, the first step of antibody discovery faces great challenges. Domestic antibody discovery technology is very backward, so I wanted to return to China and use our advanced antibody library technology to establish a company focusing on antibody discovery. In March 2016, Liu Jianghai, together with Dr. Ron Geyer, the director of therapeutic antibody resources in Saskatchewan, Canada, and angel investor Huang Qi, founded ABLINK. In 2017, the company successfully developed a new generation of "phage display antibody library" with independent intellectual property rights. In 2018, the company achieved a "hundred-billion-level" of diversity in the antibody library, becoming the antibody library with the largest diversity in China.

Completing the "hundred-billion-level diversity" antibody library theoretically allows for the discovery of antibodies against all tumor targets.

When describing the antibody library, Liu Jianghai often uses two key words: size and diversity. " Size refers to having things in the library, like fish in a pond. The bigger the size, the more fish in the pond. But if there is only one kind of fish, you can only catch one kind of fish. So, a large size can only indicate a large number of fish, but cannot indicate a lot of different types of fish," Liu Jianghai further explained. The second keyword is diversity, which means "that the fish in the pond are not only carp, yellow croaker, and osmanthus fish, but also various types of fish. This increases the variety or diversity of the fish. By 2018, the company had achieved a diversity of 10E13, that is, hundred-billion-level."

How many tumor problems can a hundred-billion level antibody library solve? "In theory, corresponding antibodies can be found for all tumor antigens, and from the current screening results, we have screened antibodies for 90% of the antigens."

 In 2016, Shengshi Junlian's fully synthetic antibody library technology was identified by the Expert Committee of Sichuan Provincial Commission of Economy and Information Technology as the highest technology level: "world advanced". From October 2016 to now, Shengshi Junlian has been committed to building an antibody library with independent intellectual property rights, including multiple fully human antibody libraries, fully synthetic antibody libraries, and nanobody libraries. At the same time, the company has also developed various other types of biologic drug libraries, including the first chimeric antigen receptor T-cell library (CAR-T library), the first T-cell receptor chimera T-cell library (TCR-T library) in China, and a billion-level diversity peptides drug library, forming a "hundred-billion level diversity" biologic drug seed library.

In addition, ABLINK is also developing its own innovative drugs. "We focus on the discovery of biopharmaceuticals, including monoclonal antibody drugs, CAR-T/TCR-T drugs, peptides drugs, small protein drugs, etc. Currently, we provide antibody screening and optimization services for multiple well-known enterprises. At the same time, we have also independently developed some new drugs, including several antibody candidates that have completed animal pharmacological tests. We plan to transfer, authorize, or jointly develop these candidates to push them towards clinical use to benefit patients.

 "I am very fortunate to settle in the Tianfu Life Science Park in Chengdu Hi-tech Zone. There are many biotech companies like us here, and we exchange ideas, learn from each other, and cooperate with each other."

In 2018, Liu Jianghai also served as a researcher at Chengdu Medical College, promoting the development of bio-pharmaceuticals through school-enterprise cooperation. "The entrepreneurial environment for biopharmaceuticals in Chengdu is very good. We met HITGEN here, a unicorn enterprise that develops chemical small molecule drug libraries, which recently went public on the Science and Technology Innovation Board. Through learning and imitation from them, we have gradually become a new biotech company that combines technology services and drug development."

Reprinted from Sichuan Online News