CAR-T & Cellular Therapy and Nk Cell Therapy
Cellular therapy with NK-cells is at a relatively early, but very promising stage of development1. Unlike T-cells, NK-cells do not need antigen sensitization to induce cytotoxicity and do not cause GvHD in the allogeneic setting2.
NK-cells can be expanded from many sources, including the bone marrow, peripheral blood, umbilical cord blood, certain cell lines, human embryonic stem cells and induced pluripotent stem cells2-4. Specific expansion protocols; for example, co-culture with genetically altered cancer cells, enable the optimal production of highly cytotoxic NK-cells5,6.
Current challenges for this therapy include the limited persistence of NK-cells in vivo and a lack of antigen specificity2. Moving forwards, the chimeric antigen receptor (CAR) genetic engineering applied to T-cells with much success is being explored in NK-cells7-11. Other strategies are also being investigated, including bi-specific killer cell engagers (BiKEs) and tri-specific killer cell engagers (TriKEs)12-14.
- Parameswaran R, Wald DN, De Lima M, et al. Novel Approach for NK Cell Therapy for Cancer. Blood. 2014 Dec; 124(21); 3836.
- Mehta RS, Randolph B, Daher M, et al. NK cell therapy for hematologic malignancies. Int J Hematol. 2018 Mar; 107(3): 262-270.
- Bock AM, Knorr D & Kaufman DS. Development, expansion, and in vivo monitoring of human NK cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). J Vis Exp. 2013 Apr; 74:e50337.
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2012 Nov 20. Identifier NCT01729091. Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma; [cited 2018 Aug 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT01729091
- Fujisaki H, Kakuda H, Shimasaki N, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009 May; 69(9): 4010-7.
- Wang X, Lee DA, Wang Y, et al. Membrane-bound interleukin-21 and CD137 ligand induce functional human natural killer cells from peripheral blood mononuclear cells through STAT-3 activation. Clin Exp Immunol. 2013 Apr; 172(1): 104-12.
- Rezvani K, Rouce R, Liu E, et al. Engineering natural killer cells for cancer immunotherapy. Mol Ther. 2017 Aug; 25(8): 1769–81.
- Carlsten M & Childs RW. Genetic manipulation of NK cells for cancer immunotherapy: techniques and clinical implications. Front Immunol. 2015 Jun; 6: 266.
- Guillerey C, Huntington ND & Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016 Aug; 17(9): 1025–36.
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2017 Feb 17. Identifier NCT03056339. Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies; [cited 2018 Aug 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT03056339
- VJHemOnc.com [Internet]. CAR T-cells vs. CAR NK-cells; c2018-06; [cited 2018 Aug 29]. Available from: https://www.vjhemonc.com/video/h1qlnnlmtja-car-t-cells-vs-car-nk-cells/
- Davis ZB, Vallera DA, Miller JS, et al. Natural killer cells unleashed: checkpoint receptor blockade and BiKE/TriKE utilization in NK-mediated anti-tumor immunotherapy. Semin Immunol. 2017 Jun; 31: 64–75.
- Felices M, Lenvik TR, Davis ZB, et al. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. Methods Mol Biol. 2016; 1441: 333–46.
- Tay SS, Carol H & Biro M. TriKEs and BiKEs join CARs on the cancer immunotherapy highway. Hum Vaccin Immunother. 2016 Nov; 12(11): 2790–6.