"There is no 'drug god' in the world. I believe that the key to innovative drug research and development is to address the needs of patients and help them find hope of life." This is Li Zonghai's biggest pursuit in his career.
As an internationally renowned pioneer in the field of CAR-T cell therapy for solid tumors, Li Zonghai has been committed to developing innovative drugs that can treat or even cure tumor patients for many years.
Li Zonghai’s pictures in this article are all provided by the interviewees
He gave up his career in medicine and chose to develop new anti-cancer drugs
Li Zonghai, who studied medicine as an undergraduate, could have become a doctor step by step A doctor, but he did not choose this path.
"There are about 14 million new cancer patients in the world every year, and there are about 4.3 million new cancer cases in China every year. As a responsible doctor, the most painful thing is seeing patients but being unable to help them. They couldn't find any effective treatment." He was helpless about this.
Li Zonghai recalled that when he was in college, a relative at home had a tumor, but there was no cure. At that time, he made up his mind to make innovative drugs with the goal of conquering the tumor.
"I was still young at that time, and I was a bit 'ignorant and fearless'. I didn't know whether I could succeed, but I wanted to at least try hard and make something valuable." Li Zonghai, master's degree student He began to engage in basic research on tumors, but he felt that he was still far away from the goal of "saving the world and saving people", and he hoped to do some work related to translational applications.
After graduating from graduate school in 2000, he first worked in a pharmaceutical factory for two years, and then entered the Shanghai Cancer Institute to pursue a doctorate, studying under the tutelage of the first batch of academicians of the Chinese Academy of Engineering and the former National 863 Biotechnology Medicine and Health Academician Gu Jianren, leader of the thematic expert group, started research on tumor gene therapy.
After graduating from the Ph.D., he established his own scientific research team at the Institute of Oncology and began exploratory research on various different tumor drug candidates, ranging from monoclonal antibodies to bifunctional antibodies, antibody drug conjugates, etc.
Starting in 2010, he gradually explored and predicted from translational research that CAR-T is one of the most likely treatments to cure tumors, so he decided to focus on the research and development of CAR-T cell therapy drugs.
Li Zonghai said that CAR-T cell therapy is a type of cellular immunotherapy that has attracted much attention among the currently popular cancer immunotherapy at home and abroad. Simply put, this therapy is to isolate T lymphocytes from the patient's body, modify them in vitro, and install them with a "GPS navigation" that can specifically identify cancer cells - Chimeric Antigen Receptor (CAR). ), these "modified CAR-T cells" are then expanded and reinfused back into the patient's body to exert a specific anti-cancer effect.
"As the scientific research team of the institute, we did not have much funds at that time, nor did we have the relevant talents and facilities to immediately promote the transformation of the project into clinical direction." Li Zonghai said frankly that the real turning point occurred when Keji was established in 2014 After biological companies, this is mainly due to the national and local governments introducing a series of initiatives to promote biomedical reform and innovation.
Early Labs.
The disease-free survival period of patients with advanced liver cancer exceeds 42 months
Since 2013, cellular immunotherapy has entered a breakthrough and rapid development stage. The top academic journal "Science" of that year "(Science) ranked it as "the first among the top ten scientific breakthroughs in the world."
Li Zonghai said that at that time, the research and development of CAR-T cell therapy drugs was not only the "patent" of international pharmaceutical giants, but top universities, scientific research institutions and biotechnology companies at home and abroad were also actively conducting related research.
In 2014, he established Keji Biomedicine (Shanghai) Co., Ltd. and served as chairman, CEO and chief scientific officer.
In the early days of starting a business, he and his team also experienced many difficulties, from setting up a laboratory and building a talent team to technology transfer and platform construction, often working around the clock and without sleep.
At the same time, in order to find more suitable targets for targeted drug development, scientific research is also racing against time. "At that time, I often needed to read hundreds of literature abstracts a day." Li Zonghai recalled that even when traveling with his family, he spent time reading literature.
In order to have more time to focus on scientific research, I still can’t drive. He said, "It is too difficult to conquer tumors. It requires concentration and perseverance to achieve it. Not driving saves time for learning and practicing driving. You can also think more attentively without driving on your way to work."
Just 7 months after the company was established, they launched two exploratory clinical studies of CAR-T for solid tumors, one of which was the world’s first CAR-T targeting EGFR/EGFRvIII dual targets. A clinical study for the treatment of brain glioma; the other is the world's first clinical study of GPC3-CAR-T for the treatment of liver cancer.
“Currently, CAR-T therapy has shown strong strength in the treatment of hematological tumors, including acute lymphoblastic leukemia, non-Hodgkin lymphoma, etc., but research on solid tumors has But there are very few, and solid tumors account for more than 90% of the tumor incidence, so we focus on solid tumors as a research direction," said Li Zonghai.
At the American Society of Clinical Oncology (ASCO) annual meeting in June 2017, he officially announced the phase I clinical study data of the liver cancer CAR-T project: among the 13 liver cancer patients treated, none Any patient developed severe toxicity; as of March 2019, 2 patients with advanced liver cancer had disease-free survival of more than 42 months.
Keji Biological Laboratory
Also carries out clinical trials for gastric cancer and pancreatic cancer
Li Zonghai’s team has set its sights on CAR-T cells in more cancer fields Treatment research.
After the establishment of Keji Company, he led the team to complete multiple rounds of tens of millions of dollars in financing. In 2017, he established a CAR-T cell preparation center in accordance with GMP (Good Manufacturing Practice) standards and began Research and development of new drugs for more cancer types; later, a subsidiary will be established in the United States, and plans to officially launch preclinical research in the United States in 2019.
In 2017, under the leadership of Li Zonghai, Keji Biotechnology cooperated with the First Affiliated Hospital of Naval Medical University to launch the world's first clinical trial of Claudin18.2-CAR-T cells for the treatment of gastric cancer and pancreatic cancer. Among the 12 patients who received treatment, 8 patients experienced varying degrees of tumor regression. Detailed research results will be announced at the 2019 American Annual Meeting of Clinical Oncology (ASCO) in Chicago, USA.
In addition to breakthroughs in solid tumors, they have also achieved good results in hematological tumors.
In 2017, Keji Biotech cooperated with many well-known domestic hospitals to launch research projects on lymphoma, multiple myeloma and other diseases. As of February 28, 2019, its human BCMA-CAR-T cells have treated 24 patients with refractory and relapsed multiple myeloma, with a complete response rate of more than 70%, and are expected to become a breakthrough therapy for this tumor.
As of March 2019, Keji Biotech, which he founded, has obtained new drug clinical trial approvals from three national food and drug administrations, and opened a CAR-T clinical trial targeting the GPC3 target at the end of March. Test kick-off meeting. This study is mainly aimed at patients with advanced hepatocellular carcinoma. Multi-center clinical trials will be carried out simultaneously in Renji Hospital Affiliated to Shanghai Jiao Tong University and the First Affiliated Hospital of Zhejiang University. In addition, research on CAR-T cell therapy for leukemia, lymphoma, and multiple myeloma is also in progress.
Li Zonghai said that in the field of innovative drug research and development, the whole world is the same and faces huge challenges.
But fortunately, the country now has strong policy support for innovative drugs. He and his team are very lucky to catch up with this era. "Now international exchanges and cooperation are more convenient, and domestic clinical approval of new drugs is also greatly accelerated. As long as we By persisting in innovation and being down-to-earth, we can harvest more and more research and development results, bring hope to more cancer patients, and make the dream of saving the world and saving lives come true. ”