East China Normal University's latest Nature article: Innovative immune cell therapy kills tumors

In the eight patients treated, the researchers observed excellent clinical safety and efficacy of PD1-19bbz

On August 31, the internationally renowned scientific journal "Nature" published online the latest research team from the School of Life Sciences of East China Normal University entitled "Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL".

This original research was completed by the team of Zhang Jiqin, Liu Mingyao, Du Bing, and Li Dali from the School of Life Sciences of East China Normal University, the Yellow River Team of the First Affiliated Hospital of Zhejiang University School of Medicine, and Shanghai Bangyao Biotechnology Co.

"Nature" senior editor Victoria Aranda commented that this research work carried out comprehensive and systematic preclinical research, successfully developed non-viral site-specific integrated CAR-T therapy, and achieved encouraging early clinical trial results

One of the reviewers, Professor Justin Eyquem of the University of California, USA, commented that this study reports the first clinical trial of PD1 downregulation of site-specific integrated CAR-T cells

5 and a half years to realize the innovation and upgrading of CAR-T technology

Zhang Jiqin, the first author and co-corresponding author of the study, associate researcher

"In the past, the idea of ​​tumor treatment was to directly kill tumor cells through drugs, but in recent years, more and more studies have found that it can kill tumors by improving the function of immune cells, and this treatment method may bring subversive effects.

In recent years, the globally popular CAR-T (Chimeric antigen receptors modified T cells, CAR-T) therapy is such an immune cell therapy

However, looking at the world, CAR-T therapy still has a lot of room for improvement at the technical level, especially at present, CAR-T cell preparation is mainly carried out by virus infection, which has high production cost, long preparation time, complicated process and potential tumorigenic risk.

"In response to these pain points, we have developed a new technical method, and through clinical trials, we have proved that the new generation of CAR-T technology we developed is safe and effective

Through extensive exploration of conditions and method optimization, the research team successfully achieved efficient integration of CAR sequences at specific sites in the genome using CRISPR/Cas9 gene editing technology

Figure: PD1 site-directed integration of CAR-T cells (red) killing cancer cells (dark blue); blue is living cancer cells, green is unedited T lymphocytes (cannot effectively remove tumor cells)

In the eight patients treated, the researchers observed excellent clinical safety and efficacy of PD1-19bbz

"We treat patients who are ineffective in traditional radiotherapy and chemotherapy or who have recurred repeatedly after treatment.

15 years from teachers and students to collaborators in joint research

Several other co-corresponding authors who participated in this innovative study can be described as a "luxurious" lineup.

"During my Ph.

From left: Du Bing, Zhang Jiqin, Liu Mingyao, Li Dali

Since 2007, East China Normal University has further deepened the discipline layout, strengthened the development of the biomedical field, clarified the main direction of attack, and invited Professor Liu Mingyao to return to China to create a new life medical research platform
.

At that time, Zhang Jiqin was graduating from Tongji University with an undergraduate degree and was admitted to East China Normal University, becoming the first graduate student of the Institute of Life Medicine
.

After graduating from a doctoral degree, Zhang Jiqin, who went to Shanghai Institute of Cancer Research, was exposed to the emerging technology of CAR-T cell therapy for the first time.
He realized that the use of gene editing tools to develop a new generation of CAR-T technology has great potential.
Therefore, he Think of the teachers at my alma mater
.

At this time, the Institute of Life Medicine of East China Normal University, relying on the platform of the Shanghai Key Laboratory of Regulatory Biology, seized the opportunity, started from nothing, and achieved rapid development, becoming a high ground for regulatory biology research with talents gathering and frequent results
.
Among them, Liu Mingyao and Li Dali's team have achieved breakthrough results in CRISPR/Cas9 gene editing
.

In 2016, in order to strengthen the construction of the scientific research team, East China Normal University established a series of new full-time scientific research positions, which also made it possible for him to return to his alma mater
.
Zhang Jiqin resolutely decided to return to the team of Liu Mingyao and Li Dali of East China Normal University.
As a full-time associate researcher, he is determined to apply gene editing technology to CAR-T and other immune cell therapy and break through the technical bottleneck
.

"The positioning of the subject must be high, and work that is breakthrough and of great significance to the development of the field must be done
.
" Zhang Jiqin remembered the words of the tutors
.

"It was very difficult when I first started doing this project, because there were relatively few people doing gene editing in T cells at that time, and there were many unknowns and difficulties
.
" I learned that Professor Du Bing's team has been working on allogeneic universal CAR-T and tumor immunotherapy.
After breakthroughs were made in the research of CAR-T, Zhang Jiqin and Professor Du Bing's team carried out in-depth cooperation, fully integrated various resources, continuously explored and optimized the cell preparation process, and finally overcame various difficulties and realized the non-viral site-specific integration of CAR- Technological breakthroughs and clinical translation
of T.

Organized research drives major original innovations

Zhang Jiqin is also a partner and vice president of R&D of Shanghai Bangyao Biotechnology Co.
,
Ltd.
In this study, the scientists from East China Normal University, who are the co-corresponding authors, have entered the company's core management as senior R&D experts of Bangyao Biology.
Professor Liu Mingyao is the founder, chairman and chief scientist of Bangyao Biology
.

"After the school did solid preliminary research, we realized that the real touchstone of this technology is still a clinical trial, so we cooperated with the First Affiliated Hospital of Zhejiang University School of Medicine and Bangyao Biotechnology to carry out a clinical trial initiated by researchers as soon as possible
.
"Zhang Jiqin said
.

In recent years, East China Normal University has continuously strengthened the deployment and connection of this in-depth cooperation by accelerating the reform of scientific research paradigms and organizational models, and implementing "organized scientific research"
.
Guide and organize innovation with policies, encourage scientific research teams and enterprises to establish non-physical research institutions, face the market, choose fields related to scientific research directions to carry out close cooperation, and promote the transfer and transformation of original scientific and technological achievements and talent training.
Under the premise of their own work, they will work part-time in the enterprise, give full play to the advantages of the school's basic research, and bring the research results to the enterprise for pilot testing and industrialization
.

Only in the field of biopharmaceuticals, East China Normal University and Shanghai Bangyao Biotechnology Co.
, Ltd.
jointly established the Shanghai Gene Editing and Disease Treatment Research Center, which has produced more than 100 patent results, and 5 projects have been initiated by researchers in 8 well-known hospitals.
Several projects have entered the clinical research stage
.

Among them, projects such as gene editing treatment for β-thalassemia, non-viral PD1 site-specific integration of CAR-T, and universal CAR-T have achieved excellent clinical results, leading the world
.

"Researchers are encouraged to deeply integrate basic research and applied research, and strive to promote the transformation of scientific and technological achievements," said Academician Qian Xuhong, president of East China Normal University.
On the one hand, in this way, outstanding scientific research talents are kept in the research team of universities to carry out scientific and technological research, and through long-term accumulation, major original innovations can be better promoted
.
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