Two major receptors involved in human natural cytotoxicity, NKp46 and NKp44, have recently been identified. However, experimental evidence suggested the existence of additional such receptor(s). In this study, by the generation of monoclonal antibodies (mAbs), we identified NKp30, a novel 30-kD triggering receptor selectively expressed by all resting and activated human natural killer (NK) cells. Although mAb-mediated cross-linking of NKp30 induces strong NK cell activation, mAb-mediated masking inhibits the NK cytotoxicity against normal or tumor target cells. NKp30 cooperates with NKp46 and/or NKp44 in the induction of NK-mediated cytotoxicity against the majority of target cells, whereas it represents the major triggering receptor in the killing of certain tumors. This novel receptor is associated with CD3zeta chains that become tyrosine phosphorylated upon sodium pervanadate treatment of NK cells. Molecular cloning of NKp30 cDNA revealed a member of the immunoglobulin superfamily, characterized by a single V-type domain and a charged residue in the transmembrane portion. Moreover, we show that NKp30 is encoded by the previously identified 1C7 gene, for which the function and the cellular distribution of the putative product were not identified in previous studies. 相似文献
Summary Recent data have substantially modified our view of natural killer cells. Although maturation of natural killer cells occurs
in the absence of a functional thymus, we have shown that clonogenic precursors capable of differentiating into mature CD3−16+56+
natural killer cells exist in CD3−4−8−16− populations isolated from human thymus. Analysis of peripheral bloodderived natural
killer clones showed that they can lyse normal cells (e.g., phytohemagglutinin-induced blasts) isolated from some individuals.
Importantly, natural killer clones isolated from single individuals displayed different patterns of cytolytic activity against
a panel of normal allogeneic cells. These data suggested the existence of a natural killer cell repertoire. A number of observations
have revealed that the expression of given HLA class I alleles protects target cells from lysis by different groups of natural
killer clones. Evidence has been gained by genetic analysis of the determinants responsible for susceptibility/resistance
to lysis by natural killer clones together with analysis, as target cells, of HLA-defective variants or HLA transfectants.
Thus, natural killer cells were found to express a clonally distributed ability to recognize HLA class I alleles. The selection
of new monoclonal antibodies directed against members of a novel family of natural killer specific p58 molecules allowed the
identification of the putative natural killer receptors for different MHC class I alleles. Firstly, a correlation was established
between the expression of given p58 molecules (e.g., EB6 and GL183) and the class I alleles recognized. Secondly, anti-p58
monoclonal antibodies restored the natural killer-mediated lysis of class I-protected cells. A similar effect was obtained
by inducing modulation of p58 surface molecules with anti-p58 monoclonal antibodies. The implications of these receptor/ligand
interactions in the physiopathological behavior of natural killer cells are discussed. 相似文献
Introduction: The lack of highly effective drugs in many malignancies has prompted scientific interest in the development of alternative treatment strategies. Cellular immunotherapy involving the adoptive transfer of immune cells that potently recognize and eliminate malignantly transformed cells has become a promising new tool in the anticancer armory. Studies suggest that the unique biological properties of umbilical cord blood (UCB) cells could precipitate enhanced anticancer activity; hence, UCB could be an optimal source for immunotherapy with the potential to provide products with ‘off-the-shelf’ availability.
Areas covered: In this review, the authors summarize data on the transfer of naturally occurring or genetically modified UCB cells to treat cancer. The focus within is on the phenotypic and functional differences compared to other sources, the alloreactive and anticancer properties, and manufacturing of these products. Therapies utilizing cytokine-induced killer (CIK) cells, natural killer (NK) cells and chimeric antigen receptor (CAR) T-cells, are discussed.
Expert opinion: The cellular immunotherapy field has become a growing, exciting area that has generated much enthusiasm. There is evidence that anticancer immunotherapy with UCB-derived products is feasible and safe; however, considering the limited number of clinical trials using UCB-derived products, further studies are warranted to facilitate translation into clinical practice. 相似文献