Immunotherapy with Cytokine Induced Killer Cells in Solid and Hematopoietic Tumors: Preliminary Data.

CIK cells are a unique population of CD3⁺CD56⁺ immune effector cells capable of lysing a broad variety of tumor cells targeted through a perforin based mechanism mediated by NKG2D.

We started a pilot clinical trial in patients with refractory lymphoma and solid tumors according to GMP guidelines that is currently ongoing.

Methods: CIK cells were generated from PBMNC and incubated in LifeCell culture bags in the presence of IFN-γ followed by IL-1β, OKT3 and IL-2. Expansion was assessed between day 21 and 28 and flow cytometric analysis was performed every week. Patients were monitored before and after treatment. Unpaired t-test was used to analyze for statistical significance. A p-value <0.05 was considered statistically significant.

Results: At present 10 patients are enrolled: 6 advanced lymphomas, 3 metastatic kidney carcinoma and 1 hepatocellular carcinoma. The median number of transferred cells per patient was 19 x10⁹ (6–37 x10⁹) and the absolute number of CD3+CD56+ cells infused ranged from 1 to 16 x10⁹ (median value 5 x10⁷/Kg). Patients affected by solid tumors received in association low doses of rhIL-2 or α-interferon. Protocol adherence was excellent and the toxicity profile was favourable. Only 2 patients developed low-grade fever during the first cycle of infusion (5%) but promptly resolved without antibiotic treatment. After CIK cell infusion, in patient’s peripheral blood the absolute median count of PBLs, CD3+, CD8+ and CD3+CD56+ cells significantly increased with a p-value of 0.034, 0.025, 0.034 and 0.038, respectively. Clinical outcome appeared promising: 2 patients had complete response (1 metastatic kidney carcinoma and 1 hepatocellular carcinoma) and 2 patients had stabilization of disease (1 metastatic kidney carcinoma and 1 NHL) with a median follow-up of 12 months (range 4–14).

Conclusions: These preliminary data showed that adoptive immunotherapy with CIK cells is a safe therapy with some suggestion of efficacy that significantly enhances immune functions increasing absolute numbers of effector cells without side effects. If confirmed in larger scale studies, these promising results may have a favourable impact on conventional treatment strategy of malignancies.