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

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.

The Present and Future of Radiotherapy

The radiotherapy market is growing due to several factors, such as an increase in the number of new cancer cases and technological advancement in the hardware and software used in radiotherapy. The current international markets are underequipped to address new cases of cancer. In low- and middle-income countries, only 10% of the population has access to radiotherapy. Therefore, there exists a wide gap between the demand and the installed base of equipment, which offers a huge opportunity for the companies to grow in the radiotherapy market. Expansion of the radiotherapy market can be both lifesaving and profitable.

Effective planning for the treatment

It is necessary, and continuous technological developments are taking place to minimize the exposure to radiation of healthy tissue, in order to avoid any side effect. This goal is a driving force of R&D for radiotherapy. Software plays an increasingly significant role in cancer care. Population growth and increased life expectancy are adding to the incidences of cancer. The software & services segment includes software, which is used for treatment planning, analysis, and services, which are needed for the maintenance and efficient use of radiotherapy devices. The software & services segment of the companies are expected to grow, as software products help improve physician engagement and clinical knowledge-sharing, patient care management, and the management of cancer clinics, radiotherapy centers, and oncology practices for better performance. Companies like Varian are continuously increasing their software portfolio. Software plays an increasingly significant role in cancer care. At the same time, healthcare systems are subject to harsh budgetary constraints in nearly every country. As a result, healthcare providers face the challenge of achieving more while using fewer resources. To achieve this goal, hospitals have a strong need for software platforms that make radiotherapy treatment cost-effective. The development of effective software will improve the delivery of advanced radiotherapy in the future.

Introduction of new technology
Technology is another salient feature. Radiation therapy remains a significant modality for cancer treatment, which is the primary driving factor for the designing of new techniques to improve the survival rate of cancer patients. New technologies, like proton beam therapy, are available in developed countries like the United States, Germany, and United Kingdom, due to well-established reimbursement policies. Proton therapy can be used on tissues that are highly sensitive, like brain, spine, and eye tumors. It is more accurate, as compared to other X-ray radiation therapies.

Advancement in the technology is also helping to execute the planning of the radiation therapy.

Technological advancement in existing technologies, such as CT imaging, is making imaging more accurate and consistent. This can give a better representation of a tumor and help in better planning. Already-existing technology, such as IMRT, SBRT, IGRT, conformal 3D, VMAT, and others that are used for radiation therapy treatment is undergoing various advancements. For example, Varian is developing a software, which can be used to develop better planning tools, in which statistical models can be used to calculate the quality of an IMRT treatment for a patient. This is expected to increase the usage of IMRT for treating cancer. IGRT is the type of radiotherapy. Research is more focused on IGRT, in order to prove its fewer side-effects. IGRT may include electronic portal imaging, fluoroscopy, ultrasound, CT scan reconstruction, and respiratory gating technology. SBRT is also growing as an option for treating cancer. SBRT is used to escalate the dose to the targeted tumor, which can increase local control while limiting the dose to nearby critical structures and normal tissues. This will cause minimum damage to the surrounding tissues and hence, will experience strong growth in the forecast period.

Struggling With Antibiotic Resistance

I never saw it coming. The process started with a small, but painful sensation right in the middle of my right butt-cheek. A very annoying problem because I am a writer squirming around as I try to fill up empty screens with words.

At first, I downplayed it as just some stupid little irritation that would go away as soon as it came. Being a diabetic for about 25 years now I am prone to inflammations and infections. This was just another in a long succession of intermittent, annoying, health problems.

At the onset, the thought never occurred that it might be an infection. I had not had any accident, no cuts, abrasions or scrapes so that did not pop up as the culprit. That is until it persisted and grew into an open sore. The pain level also rose dramatically.

I went to the doctor. He did not think it was serious. He wrote a prescription for a mild antibiotic and a cream. I left the office confident that the problem was in hand. Back home I took a pill, applied the cream and applied a bandage.

By that point sitting at my computer and performing my daily writing ritual was growing into a serious challenge. The pain was so intense that I had to force myself not to move at all. That worked for a while. I took the full antibiotic course and got into the habit of cleaning and dressing the open wound three times a day.

The process began last November. As I came to the end of the bottle of pills I was hit by a wave of disappointment and confusion. I had to face the fact that the infection had gotten worse, not better. Had the doctor misdiagnosed it? Had he given me the wrong antibiotic? Worse, did I have some rare new infection?

I went back to his office in a far more worried state than I was during my first visit. He admitted he was puzzled but brushed that aside. I got a new prescription for a stronger antibiotic that was going to require four consecutive injections.

Once again I returned home feeling a bit numb but optimistic that this stronger injectible antibiotic would do the trick. I got the injections and waited for the medication to build up in my system and wipe out the infection. I waited and waited. The situation did not get better it got even worse.

By then I could not sit and also had a hard time walking. The pain was constant even when I was trying to write while lying down. This time when I returned to the doctor’s office he told me to go to the emergency room. He would not try another antibiotic. In fact, he seemed at a loss.

Instead, I went to a clinic. The doctor there did prescribe another antibiotic, took a culture for the lab and had nurses scrub the wound. It just kept growing as if the antibiotic cream was a placebo and the injections had been nothing but water.

At that point, I had added symptoms including chronic fatigue and the first signs of depression. These two are features of a diabetic’s life and I knew what they were as soon as they arose. My immune system was beaten down and using whatever energy it could get from whatever source was available.

I did not get my hopes up during the third two-week course of the latest antibiotic. In fact, I was on pins and needles the whole time. When I finished I was not surprised that it too had failed at its job. Still, it never occurred to me that I might be antibiotic resistant.

By that point, I began to consider the possibility that my 71-year old body was running out of gas. My energy level was so low, and pain level so high that I could not write. I could only walk the short distance to the corner store to ship and my mood was buried in the pits.

When I returned to the doctor’s office he did not seem too surprised by the fact his prescription had failed. He put the lab report up on the lightbox and pointed to it. “I am afraid the results show you are resistant to every type of antibiotic we have.”

I simply could not wrap my mind around his statement. I had never thought that I had overused antibiotics to the point my immune system built up a total tolerance. Then again, nobody ever tells you where that line is.

In fact, I had taken at least one course each of the 3 previous years to cure sinus infections. I left the office completely confused and with no idea of what to do next. The doctor suggested that I schedule an operation to remove the infected area. My thought was that hospitals are great places to contract infections. I was not eager to take that option especially when it would mean I could not sit at the computer and work for a much longer period of time.

Believe it or not, that whole process went on for four months and I still had the infection. I decided to tough it out and see if my body would mobilize and get rid of it. Then I had an impulse to try one more doctor, a female who I had seen before and was impressed by.

She gave me a spray that the other doctors never mentioned, Microdacyn. This spray is a biologically active treatment for the treatment of acute and chronic wounds that are difficult to heal. I applied and applied it every day and started seeing improvement much to my relief.

My status now is guarded and uncertain. I do now I cannot afford one more sinus infection. I did discover one effective treatment, Phage Therapy. However, that is only available in Eastern Europe. I advise a very conservative approach when it comes to taking antibiotics, only do so when it is truly necessary.