How are CIK cells used in cancer bioimmunotherapy?

Biological immunotherapy for cancer is a new direction of development that deserves clinical attention. There are many components of immunotherapy, including tumor vaccines, cytokines (interleukins, interferons, etc.), immunosomal cell (CIK, DC-CIK, LAK) therapy, etc. In particular, we noticed that the internet is full of propaganda about CIK biotherapy, as if CIK cells can do everything, which feels like misleading patients. Therefore, today we combine our own experience to analyze CIK therapy from an objective scientific point of view, to give patients an understanding: First, what is CIK immune cells? CIK is an abbreviation for cytokine-induced killer, which translates to cytokine-activated killer cells. CIK cells are a type of lymphocyte, in fact, in the human blood, but the number is very small. Second, how can I get a large number of CIK cells? Theoretically, a large number of CIK cells should have a stronger anti-cancer effect. The process is a bit tedious but simple: In the first step, PBMC are extracted from the patient’s peripheral blood and centrifuged. PBMC are a large class of cells that contain small amounts of CD3+ T cells, which can be converted into CIK cells. In the second step, interferon, CD3 antibody, interleukin 2, etc. are added to the PBMC cells at different times, and after 2-3 weeks of culture, the number of cells can be expanded to 100-1000 times. This is the CIK cells, but contains a mixture of different types of cells, some of which are anti-tumor, some of which are expanded but have no anti-cancer effect. Third, CIK cells are how to fight cancer? As mentioned earlier, a large number of CIK cells are expanded in the laboratory, but only some of them are anti-cancer cells, which ones? Only cells that match the phenotype (CD3+CD56+) and also the phenotype (CD45RO+; CD27low; CD28low; CD62L-; CCR7-) will have an anti-cancer effect. In general, roughly 40% to 60% of the cells in the expanded cells meet the requirements. In addition, there is a protein called NKG2D must be present on the surface of CIK cells, because CIK depends on this protein to recognize the surface protein of cancer cells, and only first recognition can be anti-cancer. After recognizing the cancer cells, CIK can release some toxins to kill the cancer cells under the action of relevant factors in the body. Of course, CIK cells have some other ways to fight cancer. Fourth, the anti-cancer effect of CIK cells depends on what aspects? 1. Is the total number of CIK cells enough? Because CIK cells are mature cells, they will not live forever and will age. When infused into the patient for 1 to 2 weeks, the anti-cancer activity will be greatly reduced. 2. If the total number of cells is enough, is the amount of CD3+CD56+ effector cells enough? We cannot only look at the total quantity but also the quality. 3. Is the patient physically fit for treatment? After CIK cells are infused into the patient’s body, they have to rely on the body’s environment to function, and the effect will be different for different body types. 4.How big is the tumor lesion? The larger the tumor, the more cancer cells there are. If the amount of CIK cells exceeds thousands of times, what is the efficacy? 5.How is the tissue structure of the tumor? Tumors of the hematopoietic system, such as leukemia cells in a free state, easily killed by CIK cells. If it is a solid tumor, because the cancer cells are wrapped by various dense connective tissue, CIK cells are difficult to penetrate into the tumor, the effect is not good. V. What is the current clinical efficacy of CIK treatment? Nowadays, there is a lot of hype on the internet, and the anti-cancer efficacy of CIK has been blown out of proportion, but is it true? Objectively speaking, CIK cell therapy has good application prospects, but the current clinical use, the effect is still controversial. In fact, with the exception of China, most countries have not yet begun to use CIK in the clinical treatment of cancer, but are basically in the experimental stage. There are only a few documented clinical studies in Europe and the United States, and the number of people is a dozen or so. To date, there are no foreign domestic guidelines recommending the use of CIK for cancer treatment. The University of Bonn, Germany, published an authoritative article in 2011 that summarized previous global CIK clinical studies and identified 11 of these clinical trials, and found that 8 of them were done in China, and were only published in Chinese. In total, there were 426 patients, and only 3 had tumor shrinkage after CIK treatment. Although close to 24% of patients also went into remission, most of the CIK treatments in China were done in conjunction with chemotherapy and were more effective for hematopoietic tumors such as leukemia, myeloma, and lymphoma, and still less effective for solid tumors such as lung, stomach, and intestinal cancers. The article concludes that these clinical trials were very inconsistent in their design and poorly assessed for efficacy, and it is even less clear whether CIK treatment is beneficial to patients’ long-term survival. Certainly, the article holds a lot of hope for the future. Sixth, the current status of some domestic CIK therapy domestic CIK research probably began in the mid-1990s, first in Sichuan and Guangdong, and gradually in clinical use. Because the cells were cultured and expanded in the laboratory, many biological companies also smelled the business opportunity. It can be said that, in addition to individual university hospitals with specialized laboratories, most hospitals in the CIK treatment are asked to do biological companies, in fact, clinicians simply can not have the energy to do CIK cell culture, and do not understand the details of cell culture. CIK cells, is it a drug? Or is it a medical technology? If it is a drug, there should be standards and monitoring by pharmacovigilance agencies, and each patient’s CIK cells should have an individual lot number, but in practice this is not possible. If it is a medical technology, how can a company lab technician without a physician’s license and medical background do clinical care, and how can third-party quality control of CIK cells be performed to ensure patient benefit? These, again, seem reasonable and contradictory. Currently, CIK treatment has been classified as a Class III medical technology by the Health Planning Commission.