Abstract
Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-γ), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual “nature”, due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activity in vitro and in several in-vivo models, CIK cells show very limited, if any, GvHD toxicity as well as a strong intratumoral homing. For all such reasons, CIK cells have been proposed and tested in many clinical trials in cancer patients both in autologous and allogeneic combinations, up to haploidentical mismatching. Indeed, genetic modification of CIK cells as well as the possibility of combining them with specific monoclonal antibodies will further expand the possibility of their clinical utilization.
Highlights
Cytokine-induced killer (CIK) cells are non-MHC (Major Histocompatibility Complex) restricted, cytotoxic antitumoral cells expanded in vitro from circulating precursors
The expansion protocol for the generation of CIK cells, starting from peripheral blood mononuclear cells (PBMNC), lymphocytoapheresis or cord blood requires the sequential addition of 1000 U/mL human rIFN-γ on day 0 followed by 50 ng/mL monoclonal antibody against CD3 OKT3 and 500 IU/mL rIL-2 on day +1. rIL-2 and fresh complete X-VIVO medium are added every five days as detailed in the specific SOP for 14–21 days
We showed that CIK cells originate in vitro from CD56−CD8+ T cell progenitors which strongly expand upon culture in the presence of Interleukin 2 (IL-2) and acquire CD56 antigen [4]
Summary
Cytokine-induced killer (CIK) cells are non-MHC (Major Histocompatibility Complex) restricted, cytotoxic antitumoral cells expanded in vitro from circulating precursors. CIK cells share characteristics of both T and NK cells. Based on the published results obtained both in vitro and in vivo and with cells of both mouse and human origin, CIK cells show, in vivo, a very strong cytolytic activity against leukemia and graft versus leukemia (GVL), while being essentially devoid of graft-versus-host reactivity (GvHD). It has long been known that cytotoxic cells with this double T/NK phenotype are rare but present (from 1% to 5%) in circulating blood as originally described by Lanier [1], and are capable of lysing a broad array of tumor cell targets in a non-MHC-restricted manner
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