Cytomegalovirus-specific cytokine-induced killer cells: concurrent targeting of leukemia and cytomegalovirus

Chimeric antigen receptor‐engineered cytokine‐induced killer cells overcome treatment resistance of pre‐B‐cell acute lymphoblastic leukemia and enhance survival

“…A corresponding truncated CAR (CAR 63.TM) lacking intracellular signaling domains served as a control. CIK cells were generated from PBMCs of healthy donors by stimulation with IFN‐γ, IL‐2 and anti‐CD3 antibody, followed by addition of IL‐15 starting at Day 3 of the culture . One day later, CIK cells were transduced with lentiviral CAR vectors.…”

“…In a clinical setting, CIK cells have shown antitumoral activity against various solid tumors such as renal cell carcinoma, gastrointestinal and ovarian cancers, as well as different hematological malignancies . In our study, we used IL‐15‐activated CIK cells, which display enhanced cytotoxic potential when compared to CIK cells expanded in the absence of IL‐15 . This is likely due to a reduced number of T regulatory cells and downregulation of immunosuppressive IL‐35 compared to conventional IL‐2‐expanded CIK cells .…”

“…Addition of IL‐15 to the expansion culture has resulted in enhanced cytotoxicity of CIK cells, and cells generated in this fashion are currently being tested in a clinical setting . Nevertheless, while CIK cells have shown potent activity against various other cancer types, cytotoxicity against B‐ALL has been less pronounced .…”

“…[6][7][8] CIK cells are heterogeneous effector cells including T cells (CD3 1 CD56 2 ), natural killer (NK) cells (CD3 2 CD56 1 ) and natural killer T (T-NK) cells (CD3 1 CD56 1 ) that exhibit non-MHC-restricted cytotoxicity and are expanded ex vivo from peripheral blood mononuclear cells (PBMCs) in the presence of interferon (IFN)-g, anti-CD3 antibody and interleukin-2 (IL-2). 9,10 Addition of IL-15 to the expansion culture has resulted in enhanced cytotoxicity of CIK cells, 7,11 and cells generated in this fashion are currently being tested in a clinical setting. 8 Nevertheless, while CIK cells have shown potent activity against various other cancer types, cytotoxicity against B-ALL has been less pronounced.…”

Cytotoxic potential of IL‐15‐activated cytokine‐induced killer cells against human neuroblastoma cells

“…CIK cell cytotoxicity against target cells was tested by the nonradioactive Europium release cytotoxicity assay as described previously . This standard protocol was optimized for the analysis of CIK cell cytotoxicity against adherent human NB cell lines.…”