Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell

Abstract

NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase the number of NK cells in tumor target area, change the direction of NK cells, and improve their targeting ability to malignant cells. Checkpoint blocking is also a promising strategy for NK cells to kill tumor cells. Combination therapy is another strategy for improving antitumor ability, especially in combination with oncolytic viruses and nanomaterials. In this paper, the mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on. The main strategies for improving the immune function of NK cells were described, and some new strategies were proposed.

Humanized Mouse Models for the Advancement of Innate Lymphoid Cell-Based Cancer Immunotherapies

“…This enables researchers to consider thousands of drugs for cancer therapy that were previously considered too toxic to administer systemically. These drugs can be targeted to cancer cells or activated only within the TME using delivery mechanisms such as oncolytic viruses ( 162 ), coated nanoparticles ( 163 ), and ultrasound activation ( 164 ). This also increases the quantity of drugs to which the tumor can be exposed, potentially increasing their efficacy.…”

Harnessing Natural Killer Cells in Cancer Immunotherapy: A Review of Mechanisms and Novel Therapies

“…These killer cell adapters are designed by fusing the Fv domain of tumor cell antigens with the Fv domain that binds to CD16. The goal is to promote the linkage, or “immunologic synapse”, of NK cells to tumor cells via the CD16 receptor [ 22 , 56 , 57 ]. BiKEs are comprised of two antibody fragments: one targeting the tumor antigen and the other targeting CD16 on NK cells.…”

“…BiKEs are comprised of two antibody fragments: one targeting the tumor antigen and the other targeting CD16 on NK cells. TriKEs are created by integrating IL-15 into the BiKE molecule, thereby increasing NK cell cytotoxicity [ 57 ]. These have shown promise in preclinical models, and a phase I/II clinical trial is currently being conducted to evaluate their safety and efficacy in the treatment of high-risk hematologic malignancies [ 57 , 58 ].…”

“…TriKEs are created by integrating IL-15 into the BiKE molecule, thereby increasing NK cell cytotoxicity [ 57 ]. These have shown promise in preclinical models, and a phase I/II clinical trial is currently being conducted to evaluate their safety and efficacy in the treatment of high-risk hematologic malignancies [ 57 , 58 ]. Recently, a nanoparticle-based trispecific NK cell engager (named nano-TriNKE) has been developed to target EGFR receptors on tumor cells and CD16 and 4-1BB on NK cells.…”

“…These vesicles are more easily stored than the immune cells themselves and can last up to 12 months “off-the-shelf”. These characteristics make extracellular vesicles an attractive option in the delivery of cancer therapies [ 22 , 57 ]. Extracellular vesicles isolated from activated NK cells and carrying their cytotoxic proteins have shown significant suppression of tumor growth in animal models [ 85 , 86 ].…”