Interleukin-15 enhances cytokine induced killer (CIK) cytotoxic potential against epithelial cancer cell lines via an innate pathway.
CIK cells are a subset of effector lymphocytes endowed with a non-MHC restricted anti-tumor activity making them an appealing and promising cell population for adoptive immunotherapy. CIK are usually generated ex-vivo by initial priming with Interferon-γ (IFN-γ) and monoclonal antibody against CD3 (anti-CD3), followed by culture in medium containing Interleukin-2 (IL-2). Interleukin-15 (IL-15) shares with IL-2 similar biological functions and recently it has been reported to induce CIK with increased anti-leukemic potential. The aim of the study was to compare the killing efficacy of CIK generated by IL-2 alone or IL-2 and IL-15 toward tumor targets of different origins, leukemic cells and malignant cells from epithelial solid tumors. CIK bulk cultures were examined for cell proliferation, surface phenotype and cytotoxic potential against tumor cell lines K562, HL60, HeLa and MCF-7. The results showed that IL-15 is able to induce a selective expansion of CIK cells, but it is less effective in sustaining CIK cell proliferation compared to IL-2. Conversely, our data confirm and reinforce the feature of IL-15 to induce CIK cells with a potent cytotoxic activity mostly against tumor cells from epithelial solid malignancies via NKG2D-mediated mechanism.
Stem Cell and Cell Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy.
Paola
P
Iudicone
Stem Cell and Cell Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy.
Daniela
D
Fioravanti
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Elisabetta
E
Cicchetti
Department of Experimental Medicine, Sapienza University, Rome, Italy.
Ilaria Grazia
IG
Zizzari
Stem Cell and Cell Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy.
Annino
A
Pandolfi
Stem Cell and Cell Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy.
Rita
R
Scocchera
InScientiaFides Foundation, San Marino, San Marino.
Raffaella
R
Fazzina
Stem Cell and Cell Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy; Department of Experimental Medicine, Sapienza University, Rome, Italy. Electronic address: lpierelli@me.com.
Luca
L
Pierelli
D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D049109:Cell Proliferation; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000502:physiology*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D020014:K562 Cells; D061986:MCF-7 Cells; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism
D019409:Interleukin-15; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K
Cytokine-Induced-Killer; Immunotherapy; Interleukin-15; Interleukin-2