Just a tube of red blood cell therapy is expected to cure these difficult diseases
Hong Hengfei reporter Jiang Yun
There are many red blood cells, no nucleus, no genetic material, and there will be no distortion after loading the drug. It will be cleared in the liver and spleen after "long-distance running" in the body for 4 months, thus showing great potential in the treatment of rare diseases and cancer.
A few days ago, a US biotechnology company announced that the company will carry out clinical trials of erythrocyte therapy to treat cancer and autoimmune diseases, and once again absorbed nearly 100 million US dollars in financing. The company had raised hundreds of millions of dollars with erythrocyte therapy technology in 2018, when it launched a clinical trial using the technology to treat rare diseases.
In the past two years, erythrocyte therapy technology has stood out and has repeatedly become a newcomer in the field of financing. Regarding the characteristics, advantages, research status, and future industry prospects of erythrocyte therapy technology, a reporter from Science and Technology Daily interviewed relevant experts.
No nucleus and no mutation, is an ideal drug loading tool
The concave disks on both sides are like red jelly beans-this is the intuitive impression of people after seeing the microscopic image of red blood cells.
The number of red blood cells accounts for about 25% of the total amount of human body cells. Its main function is to transport oxygen and carbon dioxide. The human body produces 2 million to 3 million new red blood cells every second. Since red blood cells do not have a nucleus, they cannot replicate. Once they are produced, they will survive in the human body for about 120 days and die.
It is understood that cell therapy technology refers to the use of cells with specific functions, which are extracted by bioengineering methods and processed through in vitro expansion and special culture, so that these cells have enhanced immunity, kill pathogens and tumor cells, and promote tissue and organ regeneration It is one of the potential treatment methods for diseases in the field of life sciences.
"As a branch of cell therapy technology, chimeric antigen receptor T cell therapy (CAR-T therapy) has developed rapidly in the treatment of hematological tumors in recent years." Wu Huaxiang, director of the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Zhejiang University School of Medicine, accepted The interview stated that this therapy is to extract T cells of the patient's own immune system, after in vitro cultivation and transformation, equipped with special molecules, so that they can identify and attack specific cancer cells. "Red blood cell therapy is also a branch of cell therapy technology."
"The number of red blood cells is large, there is no nucleus, there is no genetic material, that is, there will be no genetic mutation, and there will be no distortion after loading the drug. It will be cleared in the liver and spleen after 4 months of "long-distance running" in the body." Wu Huaxiang said, CAR -T therapy treats cancer like a tracking missile, focusing T cells to quickly attack cancer cells, while red blood cell therapy technology is relatively gentle and has the characteristics of "progressive".
Researcher Li Xuejin from the Institute of Fluid Engineering, Zhejiang University said that because red blood cells are an integral part of the body, they have biocompatibility unmatched by other drug carriers. At the same time, the preparation of drug carriers using the patient's own red blood cells can minimize the body's immune rejection. . Red blood cells have unique advantages as drug carriers and are expected to become potential carriers for a variety of anti-tumor drugs, anti-viral drugs, metabolic enzymes and vaccines.
Has been exploring for many years, clinical research began to exert force
"As early as the 1970s, some scholars proposed the idea of using red blood cells as a drug carrier. At that time, due to the limitations of technical conditions, the final clinical application could not be realized." Dr. Gao Xiaofei, School of Life Sciences, West Lake University, told reporters that the past 40 Over the years, red blood cells have been explored for the delivery of many drugs, and have been validated from in vitro models, small animal models, primate models, and human clinical studies.
The reporter consulted the information and found that red blood cells were explored for drug delivery research. After decades of development and accumulation, the separated red blood cell membrane has been formed to coat the outer layer of drug-loaded nanoparticles, construct a bionic nano drug-loading system, and use red blood cells. There are several main directions for preparing extracellular vesicles to encapsulate drugs, and using intact red blood cells to directly load drugs. However, the actual application situation is not ideal. It was not until a number of domestic and foreign biotechnology companies emerged with the help of red blood cell technology in recent years that they ushered in a small peak in development.
It is understood that the complete red blood cell directly loaded with drugs can be divided into two subdivisions: internal encapsulation and external connection. Both of them have the increased vulnerability of red blood cells and the side effects that affect the interaction between red blood cells and macrophages, which can lead to the life of red blood cells. Shorten, reduce the action time of drug loading.
It is gratifying that as stem cells, gene editing and other technologies become more mature, the development of engineered red blood cell technology using stem cells as a source has accelerated. The existing red blood cell therapy platform has achieved the transformation of drawing blood from the human body and extracting the hematopoietic stem cells. After loading the drug, it will be cultured into red blood cells and imported into the body to carry out targeted treatment.
"Research on erythrocyte treatment technology at home and abroad has entered different experimental stages, for example, EryDel of Italy successfully loaded dexamethasone sodium phosphate into erythrocytes, which can treat ataxia telangiectasia. This product has entered clinical phase III Experiment." Gao Xiaofei introduced that, unlike "transforming mature red blood cells", American new biotechnology company Rubius Therapeutics has developed a set of techniques to induce mature red blood cells by inducing differentiation of hematopoietic stem cells in bone marrow in vitro . Researchers can use this technology platform, supplemented by gene editing technology, to enable these red blood cells to express a variety of key proteins. The company can replace the missing enzymes with red blood cells, and eventually hope to treat cancer and rare diseases. In my country, a number of biotechnology companies have also conducted relevant clinical studies.
Needed by emergency patients, suitable for treatment of rare diseases and metabolic diseases
Why do I need red blood cells as a drug loading system to treat certain diseases? This sounds very complicated, but it is actually due to demand, because the treatment of these diseases can not be taken orally or injected, or these two methods are not effective, so the researchers turned their attention to the field of erythrocyte therapy for a breakthrough.
Wu Huaxiang explained that at present, the pathogenic mechanism of many rare diseases has been cracked, but there are many limitations in the treatment methods. For example, enzyme drugs used to treat rare diseases such as enzyme deficiency. Enzymes are a class of organic compounds produced by living cells with a catalytic effect. Most enzymes are proteins, and a few enzymes are RNA. Proteins are easily digested, so oral administration is ineffective, and injections of foreign proteins are prone to rejection. Relying on the characteristics of large red blood cells and biocompatibility, enzyme drugs are loaded into patients, which is very suitable for the treatment of metabolic diseases and rare diseases.
For example, phenylketonuria, a rare disease, has about 120,000-150,000 patients in China. This disease is caused by the decrease or functional defect of phenylalanine hydroxylase in the human liver, which prevents the phenylalanine contained in food from being converted into tyrosine. The amino acids in the food and harmful metabolic intermediates accumulate in the blood vessels , Will damage the nervous system, and eventually lead to a decline in intelligence or even developmental cessation. This type of patient is extremely dependent on food therapy-from infancy, they can only eat low-phenylalanine or special foods that do not contain phenylalanine.
As another example, hemophilia patients have problems with blood clotting factors in their bodies, so joints, muscles, subcutaneous, and internal organs often bleed. If they do not receive adequate drug treatment, muscle atrophy, motor dysfunction, and even lifelong disability will occur. Gao Xiaofei said: "Like phenylketonuria, in theory, the transfer of coagulation factors into red blood cells can treat hemophilia patients more safely, lastingly, and effectively."
"In the future, with the maturity and perfection of red blood cell therapy technology, it will bring revolutionary changes to the treatment of certain rare diseases and metabolic diseases." Wu Huaxiang said that red blood cell therapy is an effective alternative therapy for traditional oral and injectable drugs However, regarding the treatment effect of specific diseases, more scientific research and clinical trials are needed to improve.