As a pioneer in the field of CAR-T cell therapy for internationally renowned solid tumors, Li Zonghai has been committed to developing innovative drugs that can treat or even cure cancer patients for many years.
Li Zonghai's pictures in this article are provided by the respondents.
Give up drug selection and develop new anticancer drugs.
Li Zonghai, who studied medicine as an undergraduate, could have become a doctor step by step, but he didn't choose this path.
"There are about140,000 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 to see the patient but can't help and can't find an effective treatment. " In this regard, he has no choice.
Li Zonghai recalled that when he was in college, his relatives got a tumor, but they were not cured. At that time, he made up his mind to make innovative drugs with the goal of conquering tumors.
"At that time, I was young and a little' ignorant and fearless'. I didn't know if I could succeed, but I wanted to at least work hard and make something valuable." At the postgraduate stage, Li Zonghai began to engage in basic research on cancer, but he felt that he was still far from the goal of "saving the world and saving mankind" and hoped to do some work related to transformation and application.
After graduating from graduate school in 2000, I first worked in a pharmaceutical factory for two years, and then entered Shanghai Cancer Institute to study for a doctorate. He studied under Gu, the first academician of China Academy of Engineering and the former head of the National 863 Special Expert Group on Biotechnology and Medicine and Health, and started the research on tumor gene therapy.
After graduating from Ph.D., he set up his own research team in the Institute of Cancer Research and began exploratory research on various tumor candidate drugs, from monoclonal antibodies to bifunctional antibodies and antibody drug conjugates.
Starting from 20 10, he gradually explored and predicted that CAR-T was 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 one of the most popular cancer immunotherapy at home and abroad. Simply put, this therapy is to separate T lymphocytes from patients, transform them in vitro, install a "GPS navigation" that can specifically identify cancer cells-chimeric antigen receptor (CAR), and then amplify these "modified CAR-T cells" and then transfuse them back into patients to play a specific anti-cancer role.
"As the research team of the institute, we didn't have much money at that time, and we didn't have the relevant talents and facilities to immediately promote the project to the clinical direction." Li Zonghai said frankly that the real turning point occurred after the establishment of Keji Biological Company in 20 14, which was mainly due to a series of measures introduced by the state and local governments to promote the reform and innovation of biomedicine.
Early laboratory.
The disease-free survival time of patients with advanced liver cancer is more than 42 months.
Since 20 13, cellular immunotherapy has entered a breakthrough and rapid development stage. At that time, the top academic journal Science listed it as "the top of the top ten international scientific breakthroughs".
Li Zonghai said that at that time, the research and development of CAR-T cell therapy drugs was not only a "patent" of international pharmaceutical giants, but also top foreign universities, scientific research institutions and biotechnology companies were actively conducting related research.
20 14 founded Keji Biomedical (Shanghai) Co., Ltd. as the chairman, CEO and chief scientific officer. In the early days of starting a business, he and his team also experienced many difficulties, from the establishment of laboratories and talent teams to technology transfer and platform construction, often around the clock.
At the same time, in order to find a more suitable target for targeted drug research and development, scientific research is also a matter of time. "At that time, it was often necessary to read hundreds of abstracts a day." Li Zonghai recalled that even when traveling with his family, he spent his time reading literature.
In order to have more time to concentrate on scientific research, I still can't drive. He said, "It is too difficult to conquer the tumor, and it needs concentration and perseverance to achieve it. Not driving saves time to study and practice driving, and you can think more attentively without driving on the way to work. "
Seven months after the establishment of the company, they have successively carried out two exploratory clinical studies on solid tumor CAR-T, one of which is the first clinical study on the treatment of glioma with CAR-T targeting EGFR/EGFRvIII in the world. The other is the world's first clinical study of GPC3-CAR-T in the treatment of liver cancer.
"At present, CAR-T therapy has shown great strength in the treatment of hematological tumors, including acute lymphoblastic leukemia and non-Hodgkin's lymphoma, but there is little research on solid tumors, which account for more than 90% of the tumor incidence, so we take solid tumors as the key research direction." Li Zonghai said.
At the annual meeting of American Association of Clinical Oncology (ASCO) from 2065438 to June 2007, he officially released the phase I clinical research data of CAR-T project for liver cancer: none of the 13 patients with liver cancer who were treated had serious toxic reaction; As of 2065438+March 2009, the disease-free survival time of 2 patients with advanced liver cancer has exceeded 42 months.
Science and technology biology laboratory
Clinical trials of gastric cancer and pancreatic cancer were also conducted.
Li Zonghai's team turned their attention to more research on CAR-T cell therapy in the field of cancer.
After the establishment of Keji Company, he led the team to complete several rounds of financing of tens of millions of dollars, and established CAR-T cell preparation center according to GMP (good manufacturing practice) standard in 20 17, and started the research and development of new drugs for more cancer species; After that, a subsidiary was established in the United States, and it is planned to officially launch preclinical research in the United States in 20 19.
In 20 17, under the leadership of Li Zonghai, Keji Bio cooperated with the First Affiliated Hospital of Naval Military Medical University to carry out the world's first clinical trial of Claudin 18.2-CAR-T cells in the treatment of gastric cancer and pancreatic cancer. Among the 12 patients who received treatment, 8 patients showed different degrees of tumor regression. The detailed research results will be presented at the National Annual Meeting of Clinical Oncology (ASCO) held in Chicago, USA, on 20 19.
In addition to breakthroughs in solid tumors, they have also achieved good results in hematological tumors.
From 2065438 to 2007, Keji Bio cooperated with many well-known hospitals in China to start research on lymphoma, multiple myeloma and other projects. Up to 2065438+February 28th, 2009, 24 patients with refractory and relapsed multiple myeloma have received BCMA-CAR-T cell therapy, and the complete remission rate is over 70%, which is expected to be a breakthrough therapy for this tumor.
By March 2065438+2009, Keji Bio, which he founded, had obtained three approvals for clinical trials of new drugs issued by the State Administration of Pharmaceutical Products, and a CAR-T clinical trial kick-off meeting for GPC3 target was held at the end of March. This study is mainly aimed at patients with advanced liver cancer, and will simultaneously carry out multi-center clinical trials in well-known top three hospitals such as Renji Hospital affiliated to Shanghai Jiaotong 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 under way.
Li Zonghai said that in the field of innovative drug research and development, the whole world is the same and faces great challenges. Fortunately, the national policy support for innovative drugs is very strong, and he and his team are lucky to catch up with this era. "Now international exchanges and cooperation are more convenient, and the clinical examination and approval of new drugs in China has also been greatly accelerated. As long as we persist in innovation and 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 come true. "