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On February 13th, Beijing time, Wang Jinyong Research Group of Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences published the innovative results of T-cell regeneration research online in the immunology journal Nature Immunology, which for the first time directly converted B-cells into physiologically functioning T cells through reprogramming in vivo.
this reprogramming source of T cells, both in immunodeficiency mice and in wild mice after myelin were able to quickly rebuild the T immune system and produce long-term acquired immune memory.
the results of this study provide a new perspective for re-understanding the fateal decision factors of blood lineage, as well as new theoretical guidance for the search for new sources of T-cells for cell immunotherapy. what are T-cells
T-cell immunotherapy as a new way to cure tumors? "T-cells are like 'army' in the body kingdom, whose role is to resist the invasion of 'foreign enemies' and to maintain the stability of the 'state' internally.
body produces cancer cells every day, but with T-cells close lying and clearing them, healthy people don't get tumors.
" Wang Jinyong introduced T-cells with a vivid metaphor.
said that if one day, cancer cells are disguised, or T-cell "army" combat capability is reduced, cancer cells will quickly build up to grow into tumors.
scientists around the world are trying to catch this abominable guy.
T-cell immuno-anti-tumor therapy has become a global research and clinical conversion application research focus.
"Long tumors belong to the body's internal disorder, this therapy is to suppress 'internal strife'."
", Wang Jinyong said, is a treatment that uses the cytotoxic effects of T cells (CTL) to kill tumors.
is like installing a satellite-based navigation system for the T-cell "army" to help them pinpoint their enemies and destroy tumor cells.
the treatment is becoming a new way to cure cancer, can cure melanoma, B-cell leukemia and other difficult diseases.
However, the treatment can only be modified with the patient's own immune cells, which is not suitable for infants, AIDS and other T immunodeficiency patients, and the treatment is expensive.
, these patients are not easy to form immune memory after transplantation, tumor recurrence rate of 60%.
therefore, the development of new technologies to obtain patient systogenic cells from the source of regenerative functional T cells as a possible alternative to these problems.
find "magic" to turn B-cells into T-cells At present, The world's T-cell anti-tumor therapy is taken from the patient's own peripheral blood T-cells for in vitro genetic engineering editing and amplification, the core patented technology is mainly in the hands of the United States and other Western countries.
hematopoietic stem cells are seed cells of all blood and immune cells, including T cells, and in vitro induced hematopoietic stem cell differentiation regenerative T-cell technology also faces a technical bottleneck: in vitro can not successfully simulate the t-cell development of the thymus microenvironment.
this makes it difficult for the resulting T cells to perform normal and effective physiological functions.
2012, Wang Jinyong returned from the United States to join the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences.
he boldly put forward the idea of getting around this technical bottleneck and establishing a technical platform for large-scale functional screening to obtain regenerative T cells in the body. The process of
experiment is very tortuous.
his first challenge is, where to start? "Hematopoietic stem cells have the ability to produce all the blood immune cells, so why do their offspring T-cells lose this ability?" Explain that hematopoietic stem cells must have a magical 'key'.
if you put this 'key' in the T-cell, it can also change the fate of the cell.
" he teamed up with Jilin University, Peking University, Military Medical Academy, Naval Medical University, Fujian Normal University and other scientific research teams to work together in public relations.
they screened 15 candidate transcription factors from hematopoietic stem cells, and gradually screened them, 15, 14, 13... Finally found a safe and efficient transcription factor Hoxb5, which opens the door to fate-changing factors like a key, reprogramming B cells into T-cells in the body.
2016, the technology made a major breakthrough.
this reprogramming process takes place in the body after two weeks, the thymus begins to output functional T lymphocytes, which then further mature into functional T cells.
each T cell has a B-cell-derived immunoglobulin re-chain VDJ re-removal genetic marker, and peaks at 3-4 weeks, reconstructing 50%-80% of the thymus immune output.
the experimenters followed the experimental mice for two years and found no tumor-related safety risks. Wang Jinyong,
, said that the regenerative T cells form the ability to fight memory, not only to defeat the enemy, but also to store enemy information, and later can stimulate the combat system on its own.
this method is simple, efficient and economical in theory, can produce a large number of primitive cells, produce long-term acquired immune memory, for T-cell anti-tumor therapy, AIDS and other T immunodeficiency-related diseases personalized therapy provides a new way of thinking, has great clinical transformation significance.
he said: "This technology is entirely our original.
think about it now, it's a risk.
spent a lot of money, the process was slow, and students quit in the middle.
but science needs to innovate boldly, lead the future, hope that the future can benefit the people.
", they are working with Guangzhou Medical University, Zhongshan University, Jilin University and other units, using thymus human-derived mouse animal models and non-human primate models to carry out T-cell regeneration and anti-tumor, anti-HIV infection research, if progress is smooth, it is expected that after 3 years can apply for preclinical trials of patients.
.