Cytokine-induced killer (CIK) cells have shown antitumor activity against several tumor cells both in vitro and in vivo. This study reports on the large-scale expansion of CIK cells and also present preliminary results from a pilot clinical trial. Sixteen (16) patients with renal cell carcinoma (RCC), all of whom had metastases after radical nephrectomy and adjuvant therapy using interferon-alpha (IFN-alpha) and/or interleukin-2 (IL-2), were treated with CIK cells. CIK cells were generated from peripheral blood mononuclear cells (PBMCs) and incubated in the presence of IFN-gamma followed by OKT3 and IL-2. Treatment schedule consisted of two to three cycles of CIK cell infusions at an interval of 3 weeks. A total of 46 infusions were administered to 16 metastatic RCC (mRCC) patients. The median number of transferred cells per treatment was 6.7 x 10(9) (range, 2.5-12.3). At a 60:1 effector-target cell ratio, CIK cells killed 51.4% and 32.1% of two human kidney tumor cell lines (293 and SK-RC-42), respectively. After CIK cell infusion, the percentage of CD3(+), CD8(+), CD3(+)CD56(+), and NKG2D(+) cells and the intracellular products of two type 1 cytokines (IFN-gamma and tumor necrosis factor alpha) significantly increased in the patients' PBMCs. Toxicity was minimal, and there were no immediate adverse reactions to the infusions. Three (3) patients had complete response, 1 patient had partial response, and 6 patients had stable disease. These results showed that adoptive CIK cell immunotherapy is a safe and effective treatment, which may have essential benefits for the improvement of the immunologic function in mRCC patients and play an important role in the treatment of mRCC.
Large numbers of CIK cells with greater anti-tumor activities are rapidly generated by Zol-treated iDCs/mDCs. This strategy is worthy of further investigation to improve adoptive cell therapy against tumors.
Adoptive tumor-infiltrating lymphocytes (TILs) therapy has demonstrated drastic effects on advanced malignant melanoma. Intensive pretreatment such as chemotherapy and/or total body irradiation has been used to eliminate immunosuppressive components and therefore enhances the antitumor effects of TILs. However, these pretreatments may cause severe side effects, especially for elderly patients. This case observes the complete response of how a patient with metastatic melanoma was treated sequentially with local tumor resection, postoperative adoptive cytokine-induced killer cells and TILs infusion. In addition, the cascading adoptive cell therapy was well-tolerated by the patient. Therefore, being pretreated with cytokine-induced killer cells could ameliorate the immunosuppressive condition in the patient and provide a favorable circumstance for subsequent TILs infusion. The further adoptive TILs therapy could exert the most powerful antitumor activity in such an amicable circumstance.
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