CAR-NK Cells: A Systematic Review of Emerging Alternative on Immunotherapy Against Leukemia

Background: Cancer is a public health emergency. It has a high mortality rate despite numerous studies on pharmaceutical therapies. Chimeric antigen receptor-natural killer (CAR-NK) cells are promising immunotherapy that could be used to treat cancer, especially leukemia. However, the evidence is still unclear. Thus, this systematic review aims to summarize the evidence regarding the use of CAR-NK cells as a therapy for leukemia. Method: This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. The literature search was done using PubMed, ProQuest, ScienceDirect, and EBSCOHost with “chimeric antigen receptor”, “natural killer cell”, and “leukemia” as the primary keywords until 20 March 2020. Data collection and extraction were done by three independent reviewers. Extending a risk-of-bias approach to address in-vitro studies for assessing the risk of bias was utilized in the quality assessment of the studies. Results: The search strategy identified 221 studies. Three relevant articles met our inclusion criteria. All the included studies had a low risk of bias. The main findings from available data were as follows: (a) cytotoxicities of CAR-NK cells were found highest in cell lines expressing antigen for CAR (CD19+ cancer cells) (b) CAR-NK cells had low cytotoxicities against cells that didn’t express antigen for CAR (e.g. SR-91); (c) all studies did not result in aberrant growth of the transduced CAR-NK cells. Conclusion: The use of CAR-NK cells showed promising results in treating leukemia based on its cytotoxicity against CD19+ cancer cell lines.