Discussion on Cell Therapy From The Point of Standardization, Scale, and Industrialization

By Bennie George

What is cell therapy? 
Cell therapy refers to the transplantation or input of normal or bioengineered human cells into a patient's body and newly-imported cells can replace damaged cells or involve a stronger immune killing function, so as to achieve the purpose of treating diseases. Cell therapy has shown higher application value in the treatment of cancer, hematological diseases, cardiovascular diseases, diabetes, Alzheimer's disease etc. In general, cell therapy includes tumor cell immunotherapy and stem cell therapy. There are two cell sources for cell therapy, one from the patient itself and the other from the allogeneic tissue.

The Defects of Cell Therapy 
The cell is the most basic unit that contributes to a living organism, however, it does not mean that everyone shares the same cells. On the contrary, there is a huge difference in each individual which can be compared to human-to-human differences, that is, two identical people never exist. The huge difference between cells and cell preparations is the biggest drawback of cell therapy. In this post, we will discuss several issues that need attention in the current stage of cell therapy.

Difficulties in the Standardization of Cell Therapy 
Cancer cell immunotherapy cannot be standardized from the stage of raw material acquisition. The cell treatment materiasl for each paitient are their own blood leukocytes. The condition and physical condition of each patient are different, and the collected white blood cell growth quantity and kill activity are not uniform and cannot be standardized. As it is impossible to standardize raw materials, preparation processes, and product specifications, it cannot be standardized, industrialized, and scaled up. Each tumor cell immunotherapy laboratory meets the GMP level with the hardware environment, and it can be more like a cell preparation workshop. Researchers ranged in number from a few to a dozen and could not really meet the standards of division of labor of industrialized pharmaceutical companies. Taking stem cell therapy that using umbilical cord mesenchymal stem cells as an example, which raw material is an umbilical cord, and one umbilical cord-produced cell can be utilized by many paitients. The standardization path is more advanced than the immunotherapy of tumor cells, and the raw materials can be standardized to some extent.

Difficulties in The Scale of Cell Therapy Industry 
At present, the production mode of the cell therapy industry mainly depends on technicians. In the 10,000-grade clean laboratory, the cells are operated in class 100 clean bench, cultured in a carbon dioxide incubator, centrifuged in a centrifuge, observed through an inverted microscope, and the drug reagents are stored in a medicine refrigerator. All of these devices are operated by independent biological laboratories of the individual and being linked together through the operations of scientists. This type of production model is small in scale and similar to workshop-type production. Although there are some large scales, the essence is a collection of many small workshops. Due to the small scale, the instruments used are laboratory instruments and many of the reagents used are scientific reagents, which will lead to the issue of low efficiency but high cost.

Autologous or Allogeneic 
There are two kinds of cell sources for cell therapy, one from the patients and the other from the allogeneic tissue. Autologous cell therapy cannot be standardized from the raw material acquisition stage, and it are only applied to the patient itself, the essence is essentially medical technology. The prevalence of autologous cell therapy as a medical technology is mainly due to the scale of the predicament. Allogeneic therapy, the cells derived from allogeneic. Taking tumor cell immunotherapy as an example, the cell source may be from cord blood, and the larger-scale cell source may be a filter plate for leukocyte filtration at the blood bank. Taking umbilical cord mesenchymal stem as an example, the cell source is the umbilical cord, and one umbilical cord-producing cell can be used by more than one person. If scale can be cultivated, although the quality standards cannot be quantified well, the scaled products themselves have a certain degree of standardized properties.

The cell industry, as an industry, is not the path to the advancement of cell-based therapeutics. If the advanced technology cannot be mass-produced on a large scale, it can only stay in the laboratory and become the object of research for scientists, never have achance to become a drug into the majority of patients. For allogeneic cell therapy that using allogeneic cells as raw materials, the standardized properties of the scaled products can be realized if large-scale cultures are prepared, then scale and standardization can promote each other. The current progress in standardization of cells is not easy, but the progress in scale should be relatively easy to achieve.

Natural cytokine supernatants with more standardized and standardized properties 
Cytokines are a class of small molecule proteins with broad biological activity synthesized and secreted by immune cells (such as monocytes, macrophages, T cells, B cells, NK cells, etc.) and certain non-immune cells (endothelial cells, epidermal cells, fibroblasts, etc.) Immune responses are regulated by binding to the respective receptors to regulate cell growth, differentiation and effects. Cytokines (CK) are low-molecular-weight soluble proteins that are produced by various types of cells induced by immunogens, mitogens, or other stimulants. They have the ability to regulate innate immunity [1] and adaptive immunity [2], hematopoiesis, cell growth, and damage tissue repair and other functions.

Cytokines can be divided into interleukins, interferons, tumor necrosis factor superfamily, colony stimulating factors, chemokines, growth factors etc. Cytokines form a very complex cytokine regulatory network in the body and participate in many important physiological functions of the human body. Where stem cells and immune cells cannot reach the body, cytokines can easily reach target tissue sites because of their small size.

In recent years, recombinant gene cytokines have made remarkable achievements in clinical applications as a novel biological response modifier. A large part of the effects of stem cell therapy and immune therapy arises from the action of cytokines secreted in the body. The stem cells and immune cells in the body are introduced back into the body to secrete a variety of natural structural cytokines. Although the amount of these cytokines is relatively small, they are synergistic and act directly on the cytokine network in the body because of their high natural structure activity, lack of antigenicity but diversity. Because of the standardization, standardization, industrialization, and scale of natural compound cytokines, it is more cost-effective than cell therapy, allowing more patients in need to enjoy cell-like therapeutic effects.

Although natural complex cytokines can largely replace cell therapy, but there are still conditions that require the presence of cells to exert a therapeutic effect. We hope that cell therapy can break the current situation, become high efficiency and low cost with large scale, more standardization, and then be applied to more disease treatments.

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