Five core approaches to NK cell-mediated tumor immunotherapy. (IMAGE)

China Anti-Cancer Association

Five core approaches to NK cell-mediated tumor immunotherapy.

Caption

Five core approaches to NK cell-mediated tumor immunotherapy. A. Adoptive cell therapy: Infusion of conventional NK cells or cord blood-derived NK cells; Engineering NK cells into CAR-NK cells via genetic modification; expanding and reinfusing adaptive NK cells. B. Immune checkpoint regulation: monoclonal antibodies block inhibitory receptors on NK cells. C. Immunomodulators: (a) CCR5 inhibitors suppress the CCL3 and consequently decrease MDSC infiltration. (b) Adenosine receptor inhibitors reverse functional exhaustion in TrNK cells. (c) GPR34 inhibitors antagonize LysoPS and specifically activate TrNK cells. D. Emerging strategies: (a) CRISPR-Cas9 knockout of inhibitory genes. (b) Novel engineered cells including iADAPT NK cells. (c) Innovative delivery systems such as lipid nanoparticles loaded with STING agonists. (d) Engineered cytokines exemplified by IL-15 superagonist fusion proteins. (e) Cell-derived therapies, such as extracellular vesicles from cytotoxic MLNK cells. E. Combination therapy strategies: combination treatment with targeted drugs (such as ramucirumab or sorafenib) and local treatments (such as cryoablation and radiotherapy). ADO, adenosine; CAR, chimeric antigen receptor; CCR5, C–C chemokine receptor type 5; CCL3, C–C motif chemokine ligand 3; cNK, conventional natural killer cell; CRISPR-Cas9, clustered regularly interspaced short palindromic repeats-associated protein 9; GPR34, G protein-coupled receptor 34; iADAPT, induced pluripotent stem cell-derived armored dual-adjusted and precision-engineered; LysoPS, lysophosphatidylserine; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; NKG2A, natural killer group 2, member A; PD-1, programmed cell death protein 1; STING, stimulator of interferon genes; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; TIGIT, T-cell immunoreceptor with Ig and ITIM domains; TrNK, tissue-resident natural killer cell.

Credit

Cancer Biology & Medicine

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