Disease relevance of Antibody-Dependent Cell Cytotoxicity

• PMN killed target cells by nonoxidative means, as indicated by the following observations: PMN from patients with chronic granulomatous disease (CGD), defective in their metabolic burst, lysed Raji cells normally; impairment of the oxidative metabolism of normal PMN by phenylbutazone did not affect ADCC [1].
• Antibody 2B2, which gives ADCC also in the presence of mouse lymphocytes, inhibited the outgrowth of a human melanoma in nude mice, but antibody IF4, which showed no ADCC with mouse lymphocyte effectors, did not [2].
• We have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC) [3].
• GM-CSF also induced significant ADCC in human BM macrophages against a melanoma and a lymphoma in vitro and against a lymphoma implanted in nude mice in vivo [4].
• In the present study, we investigated whether Herceptin could affect the HER-2/neu-overexpressing gastric cancer cells based on antibody-dependent cell-mediated cytotoxicity (ADCC) and compared immune effector cells from gastric cancer patients with normal individuals on ADCC [5].

High impact information on Antibody-Dependent Cell Cytotoxicity

• Here we show that a CD4 immunoadhesin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells, although, unlike natural anti-gp120 antibodies, it does not allow ADCC towards uninfected CD4-expressing cells that have bound soluble gp120 to the CD4 on their surface [6].
• Anti-CD16 antibodies block natural killer-cell mediated antibody dependent cellular cytotoxicity (ADCC) [7].
• Our data also suggest that IFN-gamma is a potent stimulator of both NK and ADCC activity [8].
• 2d of pretreatment was optimal for enhancing ADCC. rIL-4 was inactive and IL-4-depleted Con A-induced spleen lymphokine retained its ADCC-stimulating activity [9].
• Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC) [10].

Chemical compound and disease context of Antibody-Dependent Cell Cytotoxicity

• Furthermore, anti-HTLV-I Env synthetic peptide antibody-mediated ADCC identified several distinguishing HTLV-I ADCC epitopes in the middle region (amino acid residues 177 to 257) of the HTLV-I exterior glycoprotein [11].
• The data suggest that the exacerbation observed when patients with dendritic keratitis are inadvertently treated with prednisolone may be due to the steroid suppressing ADCC and not by promoting the growth of virus in the corneal cells [12].
• The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC [13].
• The 51Cr-labelled MT-1 cells after induction of HTLV-1 retrovirus by 5-iodo-2'-deoxyuridine (IdUr), showed a remarkable target sensitivity in the ADCC assay [14].
• The effects of chimeric monoclonal antibodies (cMAbs), prostaglandin E2(PGE2), and indomethacin (INDO) on antibody-dependent cellular cytotoxicity (ADCC) against human squamous cell carcinoma of head and neck (SCCHN) cell line were examined [15].

Biological context of Antibody-Dependent Cell Cytotoxicity

• By sequencing the coding regions of CRYAA, we found that a missense mutation, R116C, is associated with ADCC in this family [16].
• We have mapped an ADCC gene in family ADCC-2 to chromosome 21q22.3 near the alpha-crystallin gene CRYAA [16].
• IFN-gamma exposure caused no consistent alternations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC [17].
• We also studied effects of IFN-gamma and the synthetic glucocorticoid dexamethasone (DEX) on antibody-dependent cytotoxicity (ADCC) of chicken erythrocytes and phagocytosis of IgG-coated ox RBC by human PMN [18].
• As shown with an in vitro chromium-release cytotoxicity assay to herpes simplex virus (HSV)-infected Chang liver target cells, MC of these patients with the severe phenotype or normal MC preincubated with a combination of MAb against Mac-1 glycoprotein subunits were deficient in antibody-dependent cellular cytotoxicity (ADCC) [19].

Anatomical context of Antibody-Dependent Cell Cytotoxicity

• We identified the effector cells in human PBL that mediate IgG2a or IgG2b ADCC as nonadherent killer (K) cells [20].
• Further purification of the null cell population by filtration over nylon wool columns to reduce the number of contaminating latex ingesting monocytes did not reduce ADCC effector activity [21].
• Because a single SLE plasma could induce ADCC in T cells from several different unrelated individuals, it is unlikely that antibodies directed against particular human leukocyte antigens (HLA) or blood group antigens are involved [22].
• Monocytes and macrophages were able to utilize the chimeric IgG1 and, to a lesser degree, IgG4 and IgG3 antibodies to lyse tumor-cell targets in ADCC assays [23].
• Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-gamma was weak and inconsistent [17].

Associations of Antibody-Dependent Cell Cytotoxicity with chemical compounds

• In addition, C3-fragment-bearing cells inhibited the lysis of antibody-coated cells not concluded that target cell bound C3 fragments enhance ADCC by improving contact between target cells and those effector cells which have C3 receptors [24].
• ADCC activity was found primarily in the plastic nonadherent cell population and was greatly enriched following removal of phagocytic cells by carbonyl iron [25].
• In fact, CGD PMN had an ADCC against BCNU-treated Raji cells lower than that mediated by normal PMN, but comparable to that observed with untreated targets, and phenylbutazone reduced the lysis of BCNU-treated Raji cells by normal PMN to the level observed with the use of untreated targets [1].
• In vivo inoculations of high doses of hydrocortisone resulted in a reduction of NK activity, but ADCC was not affected [26].
• The inhibition of the Raji cell glutathione redox cycle by carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] increased cell susceptibility to PMN-mediated ADCC [1].

Gene context of Antibody-Dependent Cell Cytotoxicity

• On the other hand, PMN-mediated Lym-1 ADCC was induced or significantly augmented by various cytokines, such as GM-CSF, TNFalpha, and gamma-IFN, and chemotaxins, such as formyl peptides (FMLP), complement fragment C5a, and IL-8 [27].
• The functional activity of Fc gamma RI on PMN during G-CSF therapy was shown by measuring binding of monomeric human IgG and antibody-dependent cellular cytotoxicity (ADCC) [28].
• The resistance of Crry-expressing tumor cells to NK cell-mediated ADCC could be reversed by treatment with anti-Crry F(ab)(2) [29].
• ADCC was not prevented by inhibitory effects mediated by HLA class I. We propose that treatment with chimeric CD19 antibodies leading to ADCC by donor-derived NK cells may become a therapeutic option for the post-transplantation treatment of minimal residual B-lineage ALLs [30].
• Here we report that a chain-termination mutation in CRYBB2 is associated with ADCC in this family [31].

Analytical, diagnostic and therapeutic context of Antibody-Dependent Cell Cytotoxicity

• This was also done for the combination of the ADCC assay results plus the A or B antigen density and the direct antiglobulin test plus the titre of maternal IgG anti-A or anti-B antibodies [32].
• The resulting immunocytokine, DI-Leu16-IL-2, retained full anti-CD20 activity as assessed by fluorescence-activated cell-sorting (FACS) analysis, and had enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function relative to the DI-Leu16 antibody or control anti-CD20 antibody (rituximab) [33].
• Although decreased ADCC activity of PBMCs was observed in patients who responded poorly to conventional chemotherapy, it could be significantly augmented by the stimulation with interleukin-2 (IL-2), IL-12, or IL-15 [34].
• These results suggest that lymphokines such as IL-1 and TNF may synergize with IL-2 in the induction of ADCC and could thus potentially be useful for the immunotherapy of established tumors when combined with the administration of specific anti-tumor antibodies [35].
• These data indicate that NKR-P1bright/L.E.bright and NKR-P1bright/L.E.dim subpopulations of rat NK cells have different capacities for: 1) triggering through NKR-P1; and 2) E-A rosette formation and lysis of antibody-sensitized target cells by ADCC [36].

References