Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer

Abstract

Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and kill established tumors. One of the main challenges to the success of ACT in cancer clinical trials is the identification and generation of antitumor effector cells with high avidity for tumor recognition. Natural killer (NK) cells, cytokine‐induced killers and natural killer T cells are key innate or innate‐like effector cells in cancer immunosurveillance that act at the interface between innate and adaptive immunity, to have a greater influence over immune responses to cancer. In this review, we discuss recent studies that highlight their potential in cancer therapy and summarize clinical trials using these effector immune cells in adoptive cellular therapy for the treatment of cancer.

Immunotherapeutic Strategies for Neuroblastoma: Present, Past and Future

“…NKT-based clinical trials are ongoing for several malignancies, and are based on the injection of alpha-Galactosylceramide (α-GalCer) or α-GalCer-pulsed APC to expand NKT cells in vivo. Alternatively, autologous NKT cells have been expanded ex vivo using IL-2 and anti-CD3 mAbs [ 94 ]. Recent evidence suggested that NKT cells may have anti-tumor activities in NB patients.…”

“…γδ T cells and NK cells may represent an ideal source for adoptive cell therapy due to some shared features. Both cell types recognize and kill tumor cells irrespective of the expression of a single tumor-associated antigen, thus avoiding tumor immune escape related to single antigen loss [ 67 , 68 , 69 , 94 , 114 , 115 ]. In addition, γδ T and NK cells act through MHC-independent recognition of target cells, thus reducing the risk of alloreactivity and GvHD [ 116 ] and are able to provide immediate release of effector cytokines in different tissues.…”

Cellular immunotherapy for hematological malignancy: recent progress and future perspectives

“…Adoptive NK cell therapy refers to the introduction of ex vivo manipulated NK cells to patients for clinical use. In malignant diseases, autologous NK cell activity is inhibited largely because of the KIR ligand match, thus conferring limited clinical benefits 43 . However, NK cells from an allogeneic source have offered a promising choice for immunotherapy 44 .…”

“…NK cells have a shorter lifespan and secrete a safer cytokine profile than T cells; therefore, they might decrease the incidence and severity of adverse effects associated with autoimmunity and CRS. However, their limited persistence in vivo has also led to concerns regarding their potential efficacy 43 .…”

KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity

“…N atural killer cells are powerful effector cells in the anticancer immune response and act via direct recognition and killing of tumor cells, promotion of adaptive immune responses, and Ab-dependent cellular cytotoxicity (ADCC) (13). There is intense interest in targeting NK cells for cancer therapy via adoptive cellular therapies as well as via Ab-and cytokine-mediated stimulation (1,3,4).…”