6.4.2 Ex Vivo Expansion and Alloreactivity of CIK ...
Obtaining a sufficient number of antitumor immune cells is a critical step in the successful application of CIK cell immunotherapy.Fortunately, CIK cells can be easily expanded in vitro from peripheral blood mononuclear cells (PBMC), and some reports also showed that they could be also generated from umbilical cord blood precursors or bone marrow.The general culture protocol for the ex vivo expansion of CIK cells requires 3-4 weeks with the addition of IFN-γ, anti-CD3 antibody, and IL-2.And the detail steps are as follows: on day 0, the PBMC are separated by density-gradient centrifugation from the whole blood.Fresh medium with IL-2 is added every 2 days.After 3-4 weeks of culture, the generated CIK cells are subsequently infused back into patients.The amount of injected CIK cells varied in different studies, so did the cell expansion rate.In fact, the average final expansion rates were usually in a range of 100-fold, but individual expansion rate was described to be variable from few to more than 1,000-fold.It is well known that the more the CIK cells are injected and expanded, the better they response [98-105].(https://www.daowen.com)
Cytokine-induced killer immunotherapy, a personalized therapy that uses patients’ own PBMC to expand antitumor CIK cells which are then reinjected into patients themselves, rarely causes autoimmune response.But sometimes, it is very difficult to obtain a sufficient number of CIK cells due to the poor health situation of patients, such as elderly people and patients with immunodeficiency diseases.To solve this problem, getting CIK cells from donor PBMC seems to be an alternative option.Studies showed that CIK cells exhibited a decreased alloreactivity across HLA barriers that could further reduce the risk of graft-versus-host disease (GVHD).Many phase I clinical studies proved that infusion of the allogeneic CIK cells in patients relapsing after allogeneic hematopoietic cell transplant would reduce the incidence of GVHD events.Another solution to obtain sufficient CIK cells is collecting from the cord blood.Mature protocols have already been made for generation of cord blood-derived CIK (CB-CIK) cells.The CB-CIK cells displayed relatively lower expression of HLA, indicating a weaker immunogenicity and lower risk of GVHD.Many clinical trials proved that CB-CIK cells were effective and safe to patients with malignancies.All these suggest that CIK is a safe immune therapy with lower risk of GVHD [106-109].