Moreover, CIK cells in combination with other conventional and established therapeutic options represent an innovative approach and will probably provide a new insight into research in the future. quality control and quantity of CIK cells as well as exaggerated propaganda were constantly emerging. Thus, the Ministry of Health in China halted CIK cell therapy in May 2016, which was a major setback for the development of CIK cell-based immunotherapy. Thus, it is very important to modify technical criteria to develop a standardized operation process (SOP) and standardized system for evaluating antitumor efficacy in a safe way. (Syphilis). If the results of any of these assessments are positive, all the processes involved in the patient’s CIK cell extraction and cultivation are conducted in an isolated culture environment by specifically trained personnel. In addition, on day 11 of cell cultivation, the culture supernatants of all the CIK cells from different patients are collected for screening for bacteria, viruses, and endotoxins separately.51-53 Autologous CIK cell transfusion The autologous CIK cells are administered via intravenous infusion within a period of 30?min. The infusion of these cells is usually well-tolerated and does not cause severe adverse events such as fever, myalgia, flu-like symptoms, and fatigue.54 In general, patients receive 4C8 cycles of CIK cell infusion in a year and if the situation remains stable, more cycles of CIK maintenance treatment are given using the protocol mentioned above. Conversely, the CIK therapy is stopped if the patients do not respond well. Clinical use A growing number of clinical trials have been performed and the outcome suggests that CIK therapy yields highly compelling clinical responses in several solid carcinomas, such as hepatocellular carcinoma or B-cell malignant COCA1 lymphoma. The data of randomized clinical trials for CIK cell-based therapy were searched on PubMed and analyzed. Within the 68 matches found, 24 published papers were excluded due to the lack of clinical information and unrelated tumors and the clinical information from 44 papers34,54-97 published on CIK cell therapy was analyzed (Table?1). The patients in the immunotherapy group received at least 4 cycles of transfusion of CIK-cells, with more than 1 109 CIK cells transfused into patients within 1?h via the peripheral vein. Table 1. A summarization of the Clinical information on the CIK cell-based cancer immunotherapy.

Reference numbers Cancer disease Stage of disease Total patients(n) Patients(n) treated with CIK cells Combined with standard cancer therapy Synergism with other immunotherapy approaches Adverse reaction Intended therapeutic benefit

55-60Non-small cell lung cancerIIV529304Intravenous chemotherapyDendritic cells(DCs) with CIK cellsThe CIK cell treatment to improve the clinical outcomes of conventional chemotherapy.61Lung cancerIIV364209The CIK cells were able to improve the 2C-C HCl immune functions of patients with lung cancer.62-64Multiple myelomaIIII15278Oral & Intravenous chemotherapyDCs with CIK cellsThe DC-CIK cell therapy improved the quality of life, clinical index and survival.65,66Breast cancerIIII288148Intravenous chemotherapyDCs with CIK cellsAlleviatedThe DC-CIK cell therapy improve the quality of life.34,67-73Renal cancerIIV301160CIK cells transfected with the IL-2 gene or DCs with CIK cellsNo adverse events with grade greater than 2 were reportedThe different CIK cell-based immunotherapies 2C-C HCl would improve the immune status of patients.34,74,75Colorectal cancerIIV418388Oral chemotherapy, radiotherapy surgeryCIK cells transfected with the IL-2 gene or DCs with CIK cellsThe different CIK cell-based immunotherapies would reduce the recurrence rate and promote the survival time of patients.76,77Gastric cancerIII/IV208106Oral & Intravenous chemotherapyThe CIK cell therapy prolong DFS and improve OS.54,78-89Hepatocellular carcinomaI/II/III/IV1203650TACE and RFA or after radical resectionDendritic cells with CIK cellsThe DC-CIK cell therapy were capable of reducing recurrence, prolonging the recurrence-free span, and attacking HBV, decrease the times of TACE or RFA.90Brain cancer?2020Oral & Intravenous chemotherapyRetroNectin activated CIKsR-CIKs combined with conventional therapies could improve the prognosis of brain tumor patients34,91-93Haematopoietic tumorIIV7272Oral & Intravenous chemotherapyCIK cells transfected with the IL-2 gene or CIK cells aloneThe CIK cell therapy could significantly enhanced immune functions and increasing absolute numbers of effector cells without side effects.94,95Pancreatic cancerIV7848Oral chemotherapyThe CIK therapy was well tolerated in a second-line setting in patients with gemcitabine-refractory and advanced pancreatic cancer.96Esophageal carcinomaIIV6834RadiotherapyDCs with CIK cellshepatic and renal dysfunction, fever, allergy, and bone marrow depression were assessedThe therapy could improve patients’ quality of life and immune function, decrease bone marrow suppression, and lengthen survival time.97Nasopharyngeal Carcinoma222112Intravenous chemotherapyThe sequential CIK treatment may be effective in enhancing the therapeutic efficacy. Open in a separate window DFS, disease-free survival; OS: overall survival; TACE, transcatheter arterial chemoembolization; RFA, radiofrequency 2C-C HCl ablation. The majority of tumor patients in these clinical trials were treated with CIK cells along with conventional therapy, to achieve a synergistic antitumor effect. Other studies suggest that the cytotoxicity of CIK 2C-C HCl cells can be enhanced and improved by DC vaccination and when transfected with IL-2 gene or activated by Retro Nectin, these CIK cells demonstrate a.