Ex-vivo selection and expansion of cellular anti-tumoral lymphocyte sub-populations: cytokine-induced killer cells (CIK)

CIK cells are T lymphocytes with phenotypic and functional features similar to natural killer (NK) cells that have demonstrated a cytolytic activity not restricted to the major histocompatibility complex (MHC) towards different cancer targets. Those with preferential status were acute myeloid leukemia, chronic myelogenous leukemia and chronic lymphatic leukemia. The Laboratory studies the isolation, the ex-vivo expansion and the cytotoxic action of these cells.

CIK cells are expanded from donor’s peripheral blood by stimulation with anti-CD3 monoclonal antibodies, interleukin (IL) -2 and interferon gamma (IFN-gamma). The final preparation of CIK cells consists of a mixture of natural killer (NK), NK-like T cells and conventional T lymphocytes. NK cells are non-T and non-B lymphocytes that can be characterized as CD3- CD56+ and play a fundamental role in the defense against virus-infected cells and in cancer surveillance.

Most peripheral blood NK cells express intermediate levels of CD56 and are therefore termed "CD56 dim". A minor population (about 5%) has a high expression of CD56 and is instead called "CD56 bright". At the end of the ex-vivo CIK expansion, the NK fraction consists mainly of "CD56 bright" cells. Thus, T cells have a CD3+ CD56- phenotype, whereas NK-like T cells are a subset of T cells distinct from NK cells from the presence of the CD3 antigen and distinct from T cells by CD56 expression. As a consequence, the cell populations obtained from ex-vivo expansion can be easily distinguished on the basis of CD56 expression in two fractions.

A CD56- fraction includes T lymphocytes and a CD56 + fraction consists of CD56 bright NK cells and NK-like T cells. The three subgroups also differ in terms of proliferation, alloreactivity and cytotoxicity. In fact T lymphocytes have a high proliferative and alloreactive capacity, while the antitumor capacity is limited to NK and NK-like T. Thanks to their properties, CIK infusion obtained from donor blood has been used in prophylaxis and therapy for the relapse of leukemia in patients after hematopoietic stem cell transplantation.