NK cell-based cancer immunotherapy: from basic biology to clinical development

Abstract

Natural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives.

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

“…Other CAR-based therapies have emerged showing effectiveness in overcoming various immune escape mechanisms, including CAR-NK cells [156,157]. Moreover, specific CAR-NK cells have demonstrated effectiveness in depleting MDSCs [158].…”

Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles

“…The primary reason for the therapeutic limitation of NK cell cancer immunotherapy was attributed to the immune-suppressive TME, low activity of NK cells, inadequate homing of NK cell adoptive transfer, and limited contact frequency of NK cells with tumor cells (Figure 3) [23,43].…”

“…Those clinical trials using autologous NK cells, allogeneic NK These well-orchestrated selective cytotoxic functions of NK cells have prompted their use in many clinical trials to control tumor growth via their effector capacity. NK cell cancer immunotherapy has been considered an effective cancer treatment and a potent adjuvant to standard cancer treatment [23]. A total of 288 clinical trials are investigating NK cell immunotherapies to treat hematologic and solid malignancies in 2021 (www.clinicaltrials.…”

Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy

“…The cytokine production of NK cells is considered to be safer because the cytokines released are mainly IFN-γ and GM-CSF and once infused into patients CAR-NK cells are short lived, thereby reducing chances of other side effects on exposure. Several clinical studies have shown that NK cells do not cause GvHD [ 116 ] and safety and efficacy of NK cell therapies for hematological tumors such as AML are well established [ 128 ]. New clinical trials targeting hematological malignances are attempting to improve treatment response and NK cell number and dose.…”

“…For example, a clinical trial showed that CAR NK-92 cells can be infused at doses up to 5 billion cells per patient without causing significant adverse effects in patients with relapsed or refractory AML [ 129 ]. There are many ongoing clinical trials for both hematological and solid tumors that have not yet reported safety outcomes, but are elegantly reviewed in Liu et al [ 128 ]. Regardless, the potency of CAR-NK cells and also the method of generation and expansion of these edited cells warrant safety features as discussed below.…”