Why Are Healthy Donor CIK (NKT) Cells More Effective?
Currently, autologous CIK cells are commonly used in the clinical treatment of tumors. However, for the vast majority of patients undergoing autologous CIK cell therapy, the clinical efficacy is unsatisfactory. Data indicate that the effective rate of autologous CIK cell therapy for various malignant solid tumors is between 3.9% and 30%, averaging below 30%. Preliminary clinical results show that autologous CIK can achieve complete remission in a small number of cases, with the majority only achieving partial remission. The median survival time for treating advanced tumors is only 8.5 months.
Through clinical application, we have found that for almost all advanced tumor patients for whom methods (including autologous CIK) were ineffective, trying healthy donor CIK cell therapy still shows unexpectedly good results in some patients. Why is the effect of healthy donor CIK cells better than that of the patient’s own autologous CIK cells? A study by Professor Guo Kunyuan explains the reasons for the suboptimal efficacy of the patient’s own CIK cells. Professor Guo Kunyuan’s experimental results are:
Effector Cells | Target Cells | Killing Rate (%) |
Primary NK cells | Original K562 | 54.3 |
Veteran NK cells | Residual K562 | 16.0 |
That is to say: When immune cells and tumor cells fight for the first time, the killing activity of NK cells is 54%. When these two types of cells fight for the second time, the killing activity of NK cells is only 16%. This indicates that when NK cells and tumor cells “meet” for the second time, their killing activity decreases.
This shows that within the same body, immune cells and tumor cells become “acquaintances and friends,” and the killing effect of immune cells on tumors is greatly reduced.
Research by Dr. Hicks in the United States proves: Some healthy people’s granulocytes have very strong anti-cancer ability. The efficiency of these immune cells in fighting cancer can be up to 50 times that of ordinary people, capable of helping cancer patients fight cancer, even curing cancer.
Our own research results are: CIK cells cultured from the peripheral blood of healthy donors are significantly superior to the autologous immune cells of tumor patients in terms of both expansion speed and killing activity against tumor cells.
Cell Source | Cell Expansion (After 14 days culture) | NK Killing Activity (%) K562 | NK Killing Activity (%) LOVO |
Healthy Donor | 360 times | 92.7 | 88.8 |
Tumor Patient | 60 times | 64.2 | 53.0 |
Based on our research team’s over 20 years of experience in cell immunotherapy, cell biotherapy can be divided into three stages:
Stage | Cell Name | Culture Success Rate (%) | Clinical Effective Rate (%) |
1989-2001 | Autologous LAK | 60 | 20 |
2001-2007 | Umbilical Cord Blood CIK | 90 | 40 |
2007-Present | Healthy Donor CIK | 100 | 60 |
Our method of using healthy donor CIK cells to treat tumors is a new technology guided by the theory of tumor immunoediting, and it is also good proof of Dr. Hicks’ finding that healthy people’s immune cells have significant advantages in fighting cancer. Clinical application has already shown promising signs. The reason may be that “remote law enforcement” breaks the “tumor immunoediting,” timely mobilizing a large number of external reinforcements, concentrating efforts to eradicate the cancer. We believe this cell biotherapy technology can achieve ideal results in more clinical applications.
Advantages of Healthy Donor CIK Cells
- Fast cell proliferation speed, large quantity: In the same culture time, the proliferation speed of healthy donor CIK cells is 6 times that of tumor patients.
- Strong killing activity against tumor cells: In vitro experiments prove that the killing activity of healthy donor CIK cells against K562 and Lovo tumor cells is 1.5-2.0 times that of tumor patients.
- Wider application range: For patients whose peripheral blood counts are too low after radiotherapy and chemotherapy to use autologous CIK cell therapy, healthy donor CIK cell therapy can still be used.
For tumor patients unsuitable for the three major conventional treatments, such as the elderly and frail, those with accompanying cardiopulmonary insufficiency, or liver cancer patients complicated with cirrhosis, healthy donor CIK cell therapy can be considered. - Antiviral effect: Healthy donor CIK cells also have a significant antiviral effect. Our clinical experience shows that in liver cancer patients with high hepatitis B virus copy numbers, after treatment with healthy donor CIK cells, almost 100% of patients showed a significant reduction in HBV copies, with 60% reaching the normal range.
- Blood sugar lowering effect: In our clinical application, we found that in some tumor patients with high blood sugar, after healthy donor CIK cell treatment, blood sugar significantly decreased, and in some cases reached normal values. The mechanism warrants further study.
Adverse Reactions and Preventive Measures for Healthy Donor CIK Cells
- The most common adverse reactions are chills and fever, with an incidence of about 5%. They generally occur within 5 minutes before the end of the infusion or 1-3 hours after completion, varying with individual differences.
One situation is relatively mild, only chills, a subjective feeling of coldness, subsiding on its own in 5-10 minutes, with no discomfort. In some cases, a moderate reaction occurs, first chills then fever, with fever generally between 38-39°C, lasting 3-5 hours, resolving spontaneously without treatment. If fever reaches 39°C and persists, conventional symptomatic treatment can be applied. - Allogeneic cell reaction: Mainly manifests within the first 1-2 days after treatment as perioral edema accompanied by mild itching, which can be relieved immediately with symptomatic treatment. This phenomenon has only occurred in 2 cases. Another phenomenon is itching, redness of the skin (including facial skin) around 1 week after treatment, a pins-and-needles sensation, with psoriasis-like or scleroderma-like changes. After three days, there is a “dry cracking” phenomenon of the skin, peeling after one week. After peeling, the skin becomes whiter and finer, with no sequelae, having a cosmetic effect. This phenomenon occurs very rarely; we have only seen 1 case. Relevant experts believe that the appearance of this reaction indicates a better attack effect of the allogeneic cells on the tumor.
- How to overcome “Graft-versus-Host Disease”: The core of this technology is the infusion of allogeneic CIK cells into the patient. CIK cells are also called NK-like T lymphocytes. T lymphocytes are important effector cells for killing malignant tumors but are also the main cells causing “Graft-versus-Host Disease” (GVHD). Theoretically, infused T cells could cause GVHD.
On this issue, we take measures to reduce and avoid this risk: Based on the patient’s specific condition, formulate the optimal infusion attention and number of infusions;and Use our unique patented technology to ensure safety first.
Donor Conditions, Usage Process, and Ethical Matters
- Donor Conditions
① Age 18-30, male or female, not limited by blood type. Patient’s relatives or friends are preferable.
② Blood count WBC above 5000/mm³, lymphocytes above 20%. No infectious diseases; Hepatitis B and C virus tests qualified, HIV and Syphilis negative.
③ Flow cytometry (FCM) measurement: CD45+ cells greater than 2000/μL, natural killer activity of peripheral blood mononuclear cells against K562 greater than 80%.
- Preparation and Application Procedure
① For qualified donors after physical examination, collect 50ml of their peripheral blood mononuclear cells using an apheresis machine. Further expand and culture for 10-14 days in a GMP laboratory to prepare CIK cells with the cell number expanded hundreds to thousands of times and anti-cancer activity increased by 1.5-2.0 times or more.
② After passing quality inspection, the CIK cells are reinfused to the patient in 6 sessions. Usually once daily, 6 sessions constitute one course. Administered by intravenous drip using blood transfusion methods, drip rate 60-80 drops/minute, can be completed in 1 hour. Observe for 20-30 minutes after completion, patient can leave freely if no abnormalities. Can undergo 2-3 courses per year.
- Ethical Matters
Referring to China’s “Organ Transplant Regulations”, the allogeneic CIK cell infusion technology we carry out does not present any ethical problems, because:
① Donors are mostly the patient’s direct or collateral blood relatives or volunteers.
② It is completely based on genuine willingness, non-transactional, complying with the national spirit of voluntary unpaid blood donation.
③ Donors are healthy, checked within one month before blood collection for no infectious diseases, ensuring the recipient’s safety.
④ The mononuclear cells donated by the donor only account for about 20% of all white blood cells, having no impact on the donor’s health. Moreover, due to active white blood cell proliferation, they fully recover within one week.
⑤ It is highly significant for the patient, equivalent to inviting “divine troops” to aid in a battle where there is “no food inside and no reinforcements outside.” If the treatment outcome is as desired, the donor’s merit is immeasurable.
