6.4.4 Clinical Trials on CIK Cells
CIK as a pharmacological tool for cancer therapy has been tested in clinical trials of various tumors.90 registered clinical trials have been found on the website by searching the keywords:cytokine-induced killer cells or CIK.One trial is working on psoriasis.The majority of these are concentrated in China (58 studies), followed by 6 studies in U.S., 3 studies in Singapore, and 3 studies in Korea.Besides, two trials have been withdrawn, 1 trial terminated, 22 trials have been completed.
In a Phase I study, the safety and initial activity of CIK in therapeutic trials.In addition, CIK cells could be successfully expanded from patients treated with or without chemotherapy, so CIK cells were widely applied to treat various types of tumors including HCC, lung cancer, and gastrointestinal tumors [116].
Patients who received CIK immunotherapy after curative treatment for HCC had a 14-month median recurrence-free survival (RFS) benefit.The OS and cancer-specific survival were longer in the immunotherapy group compared to the control group.The ratio of AEs was significantly higher in the immunotherapy group (P = 0.002), but there was not a significant difference in the proportion of patients with serious AEs between groups (P = 0.15) (NCT00699816).It is worth noting that previous studies about CIK therapy for HCC showed significant benefits in preventing recurrence,but no significant survival gains.The difference of these results may be due to several aspects, such as the different intensified schedule of CIK, different cancer clinical stage or the non-standard quality of CIK cells (commercialized CIK cell compared to uncommercialized CIK cells).Adjuvant immunotherapy with activated CIK cells could increase the RFS and OS of patients who suffered with HCC (NCT00699816).Furthermore, adjuvant CIK cells treatments were proved to be safe and effective for HCC treatment by several meta-analyses [117-120].
In 2012, a phase II clinical study showed that CIK immunotherapy could enhance the efficacy of conventional chemotherapy in patients with NSCLC.Furthermore, the MHC class I-related chain A(MICA) status was also associated with the outcome measures in CIK therapy for patients with gastric cancer, for the patients with high expression of MICA were more likely to benefit from CIK therapy.In a phase II/III study, combined radiofrequency ablation with CIK has been reported to be a safe and effective treatment for CRLMs patients.Therefore, many clinical studies were conducted to evaluate the efficacy of CIK/DC-CIK cell therapy for lung cancer, and all the results showed that CIK/DC-CIK was an effective therapy for lung cancer [121-123].(https://www.daowen.com)
Many researches proved that CIK therapy was therapeutic for treatment of gastrointestinal tumors such as colorectal cancer and gastric cancer.In 2014, a meta-analysis in China showed that the combination of DC-CIK with chemotherapy could significantly improve the survival benefit, DFS rate, and overall response rate in patients with colon cancer.Furthermore, the number of CD4+ T cells was significantly increased in the DC-CIK + chemotherapy group.CIK cells could improve OS of metastatic colorectal cancer patients in a phase II clinical trial.DC-CIK combined with chemotherapy could prolong PFS and OS in colorectal cancer patients compared to chemotherapy alone.17 eligible trials including 1,735 patients are summarized with gastric cancer in a meta-analysis, and they found that the combination of chemotherapy with CIK/DC-CIK significantly increased the OS rate and DFS rate, enhanced immune function, and reduced the AEs caused by chemotherapy.The addition of CIK cells immunotherapy has shown to standard chemoradiotherapy with temozolomide improved PFS but not OS in a phase III randomized trial of newly diagnosed glioblastoma in Korea [124-126].
The clinical outcome of cancer with different pathologic stages is different, but little is known about the achievable outcome of CIK cells in patients with different pathological stages of the tumor.Combined CIK with conventional treatments could increase the survival rate of early-stage melanoma patients.So, whether the outcome of CIK is better in early-stage patient needs to be further studied [127].
As we have seen, most of the CIK registered clinical trials are restricted to Asian countries (64 trials), so it is difficult to completely evaluate the effects of CIK therapy over the world.Besides,the number of patients included in some clinical trials is also inadequate.So, more large-scale,grouped, controlled, multi-center, non-commercial clinical trials are required to confirm the immunotherapeutic effects of CIK in cancer treatment [127].