Hematological malignancies

Priming Cytokine Induce Killer (CIK) Cells for Hematological Malignancies

Curing hematological malignancies has been a great challenge for physicians and scientists for more than half century. Over the last years treatment improved resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed, due to remaining minimal residual disease (MRD). Hematopoietic cell transplantation (HCT) is an established treatment for various hematological malignancies. The efficacy of HCT relies on the effects of both high-dose chemotherapy and graft versus tumor (GVT) activity operated by the donor immune system. MRD after allo-HSCT engraftment is the reason for disease recurrence, which limit further therapeutic options. Donor lymphocyte infusion (DLI) is only effective for a limited number of diseases, and the high T cell doses required for DLI raise the risk for severe graft-versus-host-disease (GvHD). Cytokine-induced killer (CIK) cells are known to be capable of eradicating a variety of both hematological and solid malignancies in a non-MHC-restricted manner, without possessing significant alloreactive potential. In recent years, the application of CIK cells has evolved from experimental observations into early clinical studies. Activated CIK cells represent a heterogeneous population of polyclonal T cells sharing both natural killer (NK) phenotype and functional properties of NK cells. They can be efficiently expanded in vitro from peripheral blood (PB), BM mononuclear cells and umbilical cord blood by addition of interferon (IFNγ), activating antibody directed against CD3 and interleukin 2 (IL-2) or IL-15. CIK cells show a dual functional activity, retaining their original T cell specificity and acquiring during in vitro expansion an NK-like cytotoxic capacity. Priming Cytokine Induce Killer (CIK) Cells for Hematological Malignancies project is set up to enhance the cytotoxic activity of CIK cells against pediatric solid and hematological malignancies. The project is conducted by Dr. Bella Bielorai (MD) in collaboration with the clinical stem cells processing laboratory headed by Dr. Nira Varda-Bloom (PhD).  This translational research study initiated from the clinical need to develop an enhanced targeted immune therapy against aggressive solid and hematological pediatric malignancies - is an applicative project with a “bench to bedside” focus.