High Log-Scale Expansion of Functional Human Natural Killer Cells from Umbilical Cord Blood CD34-Positive Cells for Adoptive Cancer Immunotherapy

摘要: Immunotherapy based on natural killer (NK) cell infusions is a potential adjuvant treatment for many cancers. Such therapeutic application in humans requires large numbers of functional NK cells that have been selected and expanded using clinical grade protocols. We established an extremely efficient cytokine-based culture system ex vivo expansion from hematopoietic stem progenitor umbilical cord blood (UCB). Systematic refinement this two-step novel medium resulted therapeutically applicable protocol. CD56(+)CD3(-) products could be routinely generated freshly CD34(+) UCB with mean >15,000 fold nearly 100% purity. Moreover, our protocol has the capacity to produce more than 3-log frozen cells. These vivo-generated contain subsets differentially expressing NKG2A immunoglobulin-like receptors. Furthermore, UCB-derived CD56(+) by uniformly express high levels activating NKG2D cytotoxicity Functional analysis showed these efficiently target myeloid leukemia melanoma tumor lines, mediate cytolysis primary at low NK-target ratios. Our exemplifies major breakthrough producing pure limited cancer immunotherapy.