Fighting Cancer: Seeking Money, Not Killing: The Current Status of “Immunotherapy” in China After introducing the latest progress of “cancer immunotherapy” in the previous two issues, several friends asked me: My loved ones have received immunotherapy in China, but why is it ineffective? There are three facts: 1: the “immunotherapy” recently proved to be clinically effective in the United States and the “immunotherapy” currently widely used in China (mainly CIK cell therapy) are not the same thing; 2: the “CIK immunotherapy” is frying the cold food of Europe and the United States more than ten years ago, this therapy has been eliminated because of the failure of clinical trials in Europe and the United States; 3: none of the many “immunotherapy” in China has undergone rigorous clinical testing, and none of them has been approved. The company’s main goal is to provide a comprehensive range of products and services to the public. Seeking money rather than harming life is perhaps the best way to sum up immunotherapy in China. In a “money first” society, science is clearly not the most important thing. In the food industry, there are many instances of “money for life” (e.g., infant formula); in the pharmaceutical and health care fields, there are fewer instances of “money for life” due to certain regulations, but there are many instances of “money for life”. As long as the government does not act, if not dead or disabled, the risk of doing fake drugs and health products and selling buns on the street is similar. When have we ever heard of a patient suing a hospital or company purely because the treatment was ineffective, or the health care product was ineffective? For years, countless tertiary hospitals in China have been using and promoting “immunotherapy” that has been clinically proven to be ineffective, which is alarming. Hospitals and doctors, unlike businessmen, represent the full trust and hope of their patients, and it is not “ethical” to use treatments that they know are ineffective and charge high fees for them. I’m not going to discuss the loopholes in China’s regulation of “immunotherapy” here, as you’ll see if you’re interested in reading the series of articles listed in this article on Shell. I want to go back to the science and try to explain why the CIK immunotherapy currently proliferating in China is ineffective. The term “cancer immunotherapy” is a particularly vague term. In a broad sense, any method of attacking cancer cells by regulating the immune system can fall into this category, for example, attempts to treat cancer with viruses or bacteria more than 100 years ago now seem to belong to immunotherapy; in a narrow sense, there are two main categories of “immunotherapy” commonly used nowadays. The first category is cell therapy, which is to treat cancer by directly injecting activated immune cells into the patient; the second category is interventional therapy, which is to treat cancer by activating immune cells in the patient’s body through drugs or vaccines. The second type is interventional therapy, which is the activation of immune cells in the patient’s body through drugs or vaccines to treat cancer. The first generation is called LAK cell therapy, and the full name of LAk is “lymphokine-activated killer cells” in Chinese. The basic principle is to extract cells from the patient’s peripheral blood, then use “human interleukin-2” (IL-2) in vitro to induce the production of cell-killing “killer immune cells” (note that they do not specifically kill cancer cells), and finally infuse these “killer immune cells” back into the patient’s body. 20 years ago, it was reported that LAK had some effect, but the side effects were strong, and later on, large-scale clinical trials proved that LAK was ineffective. Large-scale clinical trials have proven LAK to be ineffective. The second generation is CIK cell therapy, the full name of which is “cytokine-activated killer cells”, which is similar to LAK. It is also extracted from the peripheral blood of the patient or the patient’s relatives, activated in vitro and then transfused to the cancer patient. The main difference is that in addition to “human interleukin-2”, some other factors are also added to the in vitro activation of the cells. Compared to LAK, CIK theoretically yields more and stronger “killer immune cells”. However, so far, there are no large-scale clinical trials to prove the effectiveness of CIK. The third generation is CIK-DC cell therapy, which is called “cytokine-activated killer cell-dendritic cell” hybrid therapy. Compared to CIK, CIK-DC cell therapy involves injecting not only “killer immune cells” but also “dendritic cells” into the patient’s body. Dendritic cells, named because they look like tree branches, are an important part of the immune system. Dendritic cells do not kill cells directly, but rather tell other immune cells what cells to kill, kind of like a police dog that takes police officers to arrest criminals. In CIK-DC therapy, dendritic cells are first mixed with tumor cells to sort of “smell” them, and then they are infused back into the patient along with the “killer immune cells,” which should theoretically have a greater ability to kill cancer cells. Unfortunately, so far, there are no large-scale clinical trials to prove the effectiveness of CIK-DC. The fourth generation is CAR-T, which I have been talking about recently, called “chimeric antigen receptor T-cell immunotherapy”. Recent clinical trial results in the United States look encouraging, and are expected to be approved next year for the treatment of leukemia and lymphoma. If you are interested, you can read the last two issues of the article, so I won’t go into details here. Immunotherapy in China is still stuck in the second generation of CIK therapy, a therapy that was tried and then abandoned in Europe and the US more than 10 years ago, without any clinical trials to prove its effectiveness so far. I just checked the authoritative clinical trials database, and there are only 35 CIK-related clinical trials registered and still ongoing, all in China! Is this normal? CIK therapy is not a Chinese invention, the Americans first tried it for many years, but the difference is that the U.S. clinical trials failed and could not be marketed and gave up, no one in China, so they continue to give patients with it, anyway, can sell money. Typical Chinese CIK cell therapy propaganda. Why CIK therapy is not effective? Two main reasons: one is the unknown targeting, and the other is the immunosuppression of cancer. The essence of CIK therapy is to feed the patient a large number of immune cells in the hope that they will kill the cancer cells. But there is a big problem with this: the targeting is unknown. The role of killer immune cells is very broad; they’re going to kill bacteria, they’re going to kill viruses, they’re going to kill all kinds of bad cells, and in general the vast majority of them are not going to kill cancer cells. Therefore, although CIK therapy feeds a large number of immune cells to the patient, very few of them can actually work on tumor cells, so the effect is naturally very limited. This is like we want to decorate a house, we hired 100 skilled workers, but 99 of them are excavators from Nanxiang Technical School. The emergence of third-generation CIK-DC therapy is in part to increase the targeting of CIK therapy: the hope that through the guidance of dendritic cells, so that immune cells to kill cancer cells more effectively. Unfortunately, CIK-DC therapy appears to be clinically limited because it cannot break through the second bottleneck of CIK therapy: the immunosuppression of cancer. Most cancer cells are recognized and eliminated by the immune system when they first appear, and are “killed in their infancy”, which is the body’s “immune surveillance” of cancer. This is very important, otherwise the age of cancer in humans may be decades earlier. But suddenly one day a cancer cell evolves that disguises itself well and tells the immune system, “One of us! Hold your fire!” Such a cancer cell escapes immune surveillance in order to form cancer. Therefore, all clinical cancers have evolved a way to avoid recognition by the immune system, which is called “immunosuppression” of cancer. With “immunosuppression”, no matter how many immune cells you input, it is useless. Thus, the combination of poor targeting and cancer’s natural suppression of the immune system has led to CIK, or CIK-DC, being ineffective in the majority of patients. In the last two years, two types of immunotherapies have been clinically proven to be effective for these two reasons: CAR-T therapy solves the first targeting problem by directly allowing immune cells to hit cancer cells like a missile; the second major class of effective immunotherapies specifically blocks the “immune suppression” of cancer cells, thus solving the The second problem is solved. CIK and CIK-DC are not pseudoscience, but many clinical trials have proven that they are ineffective when used alone. Theoretically, the combination of CIK (or CIK-DC) and drugs that block cancer immunosuppression (e.g. PD-1 inhibitors) should be effective. Chinese hospitals and doctors should conduct clinical trials in this area as soon as possible, instead of indulging in ineffective “immunotherapy” to generate income.