Natural killer cell‐based immunotherapy in cancer: current insights and future prospects

Abstract

Abstract. Sutlu T, Alici E (Karolinska Institutet, Stockholm, Sweden). Natural killer cell-based immunotherapy in cancer: current insights and future prospects (Review). J Intern Med 2009; 266: 154-181.As our understanding of the molecular mechanisms governing natural killer (NK) cell activity increases, their potential in cancer immunotherapy is growing increasingly prominent. This review analyses the currently available preclinical and clinical data regarding NK cell-based immunotherapeutic approaches in cancer starting from a historical background and an overview of molecular mechanisms taking part in NK cell responses. The status of NK cells in cancer patients, currently investigated clinical applications such as in vivo modulation of NK cell activity, ex vivo purification ⁄ expansion and adoptive transfer as well as future possibilities such as genetic modifications are discussed in detail.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Other apoptotic-inducing mechanisms of NK cells, such as antibody-dependent cellular cytotoxicity, Fas ligand and tumor necrosis factor (TNF)-α secretion, have been discovered [70,71]. In addition to direct cytotoxicity, NK cells play an important role in the regulation of the anti-tumor adaptive immune response because they produce cytokines such as interferon-γ, TNF-α, interleukin (IL)-10, and several chemokines and growth factors.…”

Ex Vivo Generated Natural Killer Cells Acquire Typical Natural Killer Receptors and Display a Cytotoxic Gene Expression Profile Similar to Peripheral Blood Natural Killer Cells

“…Due to their strong ability to target tumor cells, NK cells have been described as promising effectors for adoptive immunotherapy of cancer [7]. So far, NK cells for adoptive transfer have mainly been generated through ex vivo expansion of PBNK cells [8]. Obtaining adequate purity and cell numbers of functional NK cells remains the biggest challenge for their therapeutic use.…”

NK cell-based immunotherapy for malignant diseases

“…[89][90][91] Combining IL-2 and IFN-a with GM-CSF has been shown to be effective, providing a solid basis for using IL-2 to stimulate antitumor activity from endogenous NK cells. 60 Other NK cell activators, such as IL-12, IL-15, IL-18 and IL-21, have been successfully tested in preclinical cancer models as part of various vaccination strategies. 92,93 In the presence of IL-15 and hydrocortisone (HC), autologous NK cells can be activated and expanded in vitro, and these cells are effective in vivo in a lung metastasis mouse model which accumulated in lung tissue and were retained in the tumor-bearing site for more than 3 days.…”