Treating diseases with stem cells: A new opportunity for treatment

Excerpted from Hong-Nerng Ho, Professor Emeritus of the National Taiwan University College of Medicine and General Counsel of Taipei Medical University

July 2019 Taiwan's "Good Heart" 《好心臟》magazine "Cell therapy is open to the public, autologous immune cells can be used as anti-cancer antidote"

資歷｜
何弘能教授
臺灣大學醫學院婦產科名譽教授
臺灣大學附設醫院婦產部顧問醫師
樂迦再生科技股份有限公司董事長
臺北醫學大學醫學院講座教授
台北市立萬芳醫院婦產部主治醫師
臺灣大學醫學系醫學士
美國匹茲堡大學病理部研究員
美國加州大學洛杉磯分校內科研究員
臺灣醫學會理事長 2016-2019
臺大醫院院長 2015-2019
臺灣婦產科醫學會理事長 2013-2016
國際細胞治療學會副理事長(亞太區域) 2013-2015
臺灣幹細胞學會理事長 2009-2013
臺灣生殖醫學會理事長 2006-2008
美國生殖免疫學會副理事長 1998-2000

Immunotherapy (especially immune checkpoint inhibitors), which is regarded as a new breakthrough in cancer treatment, is still in its infancy. Recently, autologous immune cell or stem cell therapy has become another wave of popularity. What exactly is cell therapy?
Cell therapy also includes the use of cells from other species. In 2019, Taiwan's "Regulations on the Implementation or Use of Specific Medical Technology Inspection and Testing Medical Equipment" opened up "autologous cell" (including autologous immune cells or autologous stem cells, etc.) therapy, because the use of other people's allogeneic cells is prone to rejection, immune disorder, infectious diseases, etc., and the risks are relatively high.
However, at present, Taiwan's autologous stem cells only allow adult stem cells, not embryonic stem cells. This is because embryonic stem cells have strong differentiation capabilities and many uncertainties, and require separate regulations. Therefore, they are not included in the "Special Management Measures".

Japan has many years of experience in autologous immune cell therapy

In summary, the most popular one is autologous immune cell therapy, which is another life-saving hope for some cancer patients who have not responded well to existing therapies.

Cancer treatment generally starts with surgical resection. If surgery is not possible, there are other options such as chemotherapy, radiotherapy, and targeted drugs. However, cancer cells are too smart and will continue to evolve, so controlling cancer cells requires more effective weapons. A long time ago, studies have suggested that when the body's own immune cells are strong enough, they can kill cancer cells. In theory, using one's own cells will have fewer side effects and can eliminate the evil completely to reduce the recurrence of cancer cells. Therefore, immune cells have always been one of the methods for treating cancer.

In fact, immune cell therapy has been practiced in foreign countries for many years, especially in Japan. Because the clinical trial regulations are more relaxed, cell therapy has been implemented in Japan for many years. However, because Taiwan's regulations have not kept up, immune cell therapy has not developed, resulting in patients who want to seek this treatment having to seek medical treatment across the ocean.

In 2019, Taiwan opened up six types of autologous immune cell therapies, which are relatively safe, have fewer side effects, and have some evidence in the literature, including NK, DC, CIK, DC-CIK, TIL, and gamma-delta T immune cells; the target patients are patients with hematological malignancies or stage I to III solid cancers who have not responded to standard treatment, as well as patients with stage IV solid cancer. Currently, blood tumors are the most effective.

Immune cells cultured in vitro and then injected back into the body to destroy cancer cells

Autologous immune cell therapy involves removing the patient's immune cells, culturing, inducing, activating and expanding them, and then injecting them back into the patient's body to fight cancer cells. There are many types of immune cells. The earliest research used Natural Killer Cells (NK). The test subjects started with melanocytoma (a type of skin cancer). The initial results were good, but later it was discovered that cancer cells are not that stupid and can adjust at any time. NK cells, which are the vanguard of immune cells, have poor ability to identify "enemies", especially cancer cells are very good at camouflage. When NK cells do not have sufficient number or specificity, they may not be able to kill cancer cells.

Immune cell cancer treatment varies greatly among individuals and there are many unknowns

Although immune cell therapy is a new and emerging anti-cancer medicine, the effects of immune cell therapy on patients vary greatly from patient to patient. Because cell culture processing is not as relatively stable as single drugs, is it possible that infection or harmful chemicals could enter during the process? What will happen when immune cells are cultured in large quantities and injected back into the body? It often varies from person to person and there is a lot of uncertainty.

The opening of autologous cell therapy in Taiwan not only provides a glimmer of hope for cancer patients, but also helps to collect more data for analysis. This will allow us to more clearly understand what kind of patients have a greater chance of success with this therapy, thus achieving so-called precision medicine. There are also controls on the cost. Currently, several medical centers have proposed plans that one course of treatment will cost around NT$2 million (approximately HK$470,000).

The quantity and quality of immune cell expansion are also key to the success of treatment

For immune cell therapy to be successful, the key is to choose which immune cells to use, which cancer to use, and the patient's own condition. In addition, every process and link in the laboratory will also affect the effect, so immune cell therapy is difficult to conduct clinical trials, which is not as simple and clear as drug clinical trials.

In particular, after immune cells are extracted from the patient's blood, they need to undergo an in vitro culture process in order to increase the number of immune cells. This method of "strengthening the immune cells" involves many technologies and affects the quality of the immune cells. For example, whether it is artificial cultivation or automated cultivation by machine, which specific cytokines to use, etc., each hospital and biotechnology company has different practices, and we hope to have more control in the future.

Immune cell therapy is administered approximately once a month, and a course of treatment lasts for 3 to 6 months. The course of treatment or anti-cancer effect varies from person to person, and may have different results for different cancers and different stages. However, immune cell therapy can also be used as an adjuvant therapy after surgery or chemotherapy to reduce the chance of cancer recurrence or metastasis. Just like immune checkpoint inhibitors, they are rarely used alone as anti-cancer drugs, but are used in combination with other treatments to fight cancer together.

Therefore, some studies later switched to using dendritic cells (DC). Dendritic cells with spikes play the role of "scouts" that can search and identify cancer cells, and then command combat-capable T cells to go to the battlefield to kill the enemy. Although this does increase the anti-cancer effect, it was later discovered that it was only about 10% to 30% effective. So some studies tried "cocktail therapy", which is to use these immune cells together, but the effect is still limited.

High hopes for stem cell potential

In addition to immune cells, the medical community also has high expectations for stem cell therapy. Once successful, it will bring revolutionary changes to medical care. For example, if a patient with heart failure needs a heart transplant to save his life, since there are limited heart donors, if stem cell therapy can achieve the same effect as "replacing parts", the survival rate will increase significantly. However, despite the global investment in stem cell research, no major results that can be applied clinically have yet emerged.

Japan is a global leader in the field of iPS cells (also known as induced pluripotent stem cells or omnipotent cells). This was first successfully developed by Kyoto University professor Shinya Yamanaka. It took only six years from the publication of his paper to winning the Nobel Prize, which shows the ambition of the Japanese government. There are now many clinical trials using iPS cells to treat retinal, heart, spinal and other diseases.

As for embryonic stem cell research, because it involves ethical issues in the United States, related research development has been stop-and-go. In the early days, the US government did not allow research on embryonic stem cells. It was not until 2009 that Obama approved clinical trials using embryonic stem cells to treat patients with spinal injuries. Later, similar trials were conducted for retinal treatments, but these two projects were not successfully promoted due to reasons such as being too expensive.

Adult stem cells are relatively safe

Therefore, so far, whether it is embryonic stem cells or pluripotent cells, although the future looks bright, the research is still in the experimental stage. The ones currently available for use are autologous adult stem cells. Although their differentiation ability is not as strong as that of embryonic stem cells or omnipotent stem cells, they are relatively safe and can avoid canceration due to poor control. Another advantage is that they are relatively cheap and easy to obtain, and do not have the ethical controversy of using embryonic stem cells.

Cell therapy may one day become a new hope for saving lives for cancer patients.

References and Excerpted

July 2019 Taiwan's "Good Heart" 《好心臟》magazine