Abstract
Cytokine-induced killer (CIK) cells are a heterogeneous population of immune effector cells that feature a mixed T- and Natural killer (NK) cell-like phenotype in their terminally-differentiated CD3+CD56+ subset. The easy availability, high proliferation rate and widely major histocompatibility complex (MHC)-unrestricted antitumor activity of CIK cells contribute to their particularly advantageous profile, making them an attractive approach for adoptive immunotherapy. CIK cells have shown considerable cytotoxicity against both solid tumors and hematological malignancies in vitro and in animal studies. Recently, initial clinical experiences demonstrated the feasibility and efficacy of CIK cell immunotherapy in cancer patients, even at advanced disease stages. Likewise, the clinical application of CIK cells in combination with standard therapeutic procedures revealed synergistic antitumor effects. In this report, we will focus our consideration on CIK cells in the treatment of hematological malignancies. We will give insight into the latest advances and future perspectives and outline the most prominent results obtained in 17 clinical studies. Overall, CIK cells demonstrated a crucial impact on the treatment of patients with hematological malignancies, as evidenced by complete remissions, prolonged survival durations and improved quality of life. However, up to now, the optimal application schedule eventually favoring their integration into clinical practice has still to be developed.
Highlights
Over the last few decades, considerable progress has been made in the treatment of hematologic malignancies
Major advances have been made in the field of adoptive immunotherapy, which has been considered a promising approach in taking advantage of the stimulated patient’s immune system to recognize and eventually eliminate tumor cells
Cytokine-induced killer (CIK) cells emphasize these natural abilities of the human immune system to destroy cancer cells and, represent a unique immunotherapeutic approach, which enriched our therapeutic repertoire in the struggle against cancer
Summary
Over the last few decades, considerable progress has been made in the treatment of hematologic malignancies. An increasing number of clinical trials have reported that the adoptive CIK cell transfer revealed considerable antitumor efficacy and led to both significantly improved progression-free and overall survival (OS) in patients bearing different, especially solid, types of cancer, while being without serious side effects and well tolerated by the patients. CIK cells meet decisive requirements to be effective in an immunotherapeutic approach These cytotoxic CD8+ T-cells, known as natural killer (NK) cell-like T lymphocytes, expand more rapidly and exhibit a stronger anti-tumor activity than other reported immune effector cells [3,9]. Heninger et al [21] reported on similar results showing that the cultivation with IL-7 leads to a higher proliferation rate and cytotoxicity as compared to solely IL-2 expanded CIK cells This observation was accompanied by a highly abrogated immunosuppressive Tregs function. CD3+CD56+ cells in the amplified population, while the interactions between DCs and CIK cells led to an increase of the IL-12 secretion [26,27,28,29,30]
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