Cytokine effects and role of adhesive proteins and Fc receptors in human macrophage‐mediated antibody dependent cellular cytotoxicity

Liesveld, Jane L.; Frediani, Karen E.; Winslow, J M; Abboud, Camille N.; Duerst, R.

doi:10.1002/jcb.240450412

Cited by 29 publications

(10 citation statements)

References 32 publications

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“…In contrast to other studies in this field (Capone et al, 1984;Hagan et al, 1986; (Velders et al, 1995 (Velders et al, 1996). In agreement with Herlyn et al (1985), our results, as presented in Figure 2, (Velders et al, 1996) The requirement of accessory adhesions between effector and target for ADCC is not very clear, however the scope of the publications on the subject suggests their importance (Liesveld et al, 1991;Webb et al, 1991;Edwards et al, 1992; Kushner and Cheung, 1992 [owing to their chimerization using the same genes for the constant Ig chains (Sun et al, 1987;Velders et al, 1994)], it is the affinity of the antibody to the target antigen or the three-dimensional orientation of Fc tails that is of importance. From the results presented in Figure 4 we conclude that high MAb affinity, or a large number of antibody-antigen interconnections between effector and target cells, may well compensate the reducing effect on ADCC of the suppressed accessory interactions.…”

Section: Adcc Kinetics and Mab Affinitysupporting

confidence: 92%

The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas

Velders

Rhijn²,

Oskam³

et al. 1998

Br J Cancer

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Summary Antibody-dependent cellular cytotoxicity (ADCC) is considered to be the major mechanism through which tumour cells, upon treatment with anti-tumour MAbs, are eliminated in vivo. However, the relative importance of various parameters that influence the efficacy of ADCC is unclear. Here we present in vitro data on the impact of MAb affinity and antigen density on ADCC, as obtained by comparison of two MAbs against the tumour-associated antigen Ep-CAM. The low-affinity MAb 17-1A (Ka = 5 x 107 M-1) currently used for therapy, and the highaffinity MAb 323/A3 (Ka = 2 x 109 M-1), were compared in ADCC experiments against murine and human tumour target cells transfected with the Ep-CAM cDNA under the control of an inducible promoter to enable regulation of the target antigen expression levels. Data obtained from these studies revealed that the high-affinity MAb, in contrast to the low-affinity MAb, could mediate killing of tumour cells with low antigen expression levels. Even at comparable MAb-binding levels, ADCC mediated by the high-affinity MAb was more effective. The kinetics of ADCC was also found to be determined by the level of antigen expression, and by the affinity and the concentration of the MAb used. The efficacy of ADCC with both low-and high-affinity MAbs further depended on adhesive interactions between effector and target cells mediated by CD1 8. However, at every given MAb concentration these interactions were of less importance for the high-affinity MAb than for the lowaffinity MAb. As heterogeneity of a target antigen expression is a common feature of all tumours, and some tumour cells express very low levels of the antigen, the use of high-affinity MAbs in immunotherapy may significantly improve the clinical results obtained to the present date in the treatment of minimal residual disease.

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Section: Adcc Kinetics and Mab Affinitysupporting

confidence: 92%

The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas

Velders

Rhijn²,

Oskam³

et al. 1998

Br J Cancer

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“…Phagocytosis was studied after differentiation of MDM in medium supplemented with human recombinant cytokines that have been shown to modulate macrophage function (24,29,30). We observed significant Fc␥RI-mediated phagocytosis (H22 ϫ 520C9) under all conditions (Fig.…”

Section: Resultsmentioning

confidence: 76%

Differential Effect of Cytokine Treatment on Fcα Receptor I- and Fcγ Receptor I-Mediated Tumor Cytotoxicity by Monocyte-Derived Macrophages

Keler¹,

Wallace

Vitale³

et al. 2000

The Journal of Immunology

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Macrophages represent an important effector cell for Ab-mediated tumor therapy. Previous studies have documented that cytokines can influence Fc receptor (FcR) expression and function. In this study we examined the tumoricidal activities of the type I receptors for IgG (FcγRI) and the IgA FcR (FcαRI) on monocyte-derived macrophages (MDM) cultured in the presence of IFN-γ, M-CSF, or GM-CSF. Bispecific Abs were used to target a Her2/neu breast carcinoma cell line, SKBR-3, to FcαRI or FcγRI on MDM. Although FcαRI and FcγRI share a common signaling pathway contingent on association with the γ-chain (FcRγ subunit), a marked difference in their efficiency in mediating tumoricidal functions was seen in response to specific cytokines. M-CSF- and GM-CSF-treated MDM mediated efficient phagocytosis of SKBR-3 cells by FcαRI and FcγRI; however, IFN-γ-treated MDM phagocytosed tumor cells only with the FcγRI-directed bispecific Abs. Similarly, IFN-γ-cultured MDM lysed tumor cells more efficiently via FcγRI then by FcαRI as measured in Ab-dependent cellular cytotoxicity assays. Conversely, GM-CSF-treated MDM mediated more efficient lysis of tumor cells via FcαRI than FcγRI, while M-CSF-cultured MDM were relatively less efficient in mediating Ab-dependent cellular cytotoxicity through either receptor. With the exception of IFN-γ-mediated enhancement of FcγRI expression and FcγRI γ-chain complexes, the regulation of FcγRI- or FcαRI-mediated activity occurred without significant change in either receptor expression or total complexes with γ subunit. These data suggest that the efficiency of Ab-mediated tumor therapy, which depends on FcR effector cell functions, may be modified by the use of specific cytokines.

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“…These biological activities include the ability to stimulate the proliferation and differentiation of multipotential bone marrow progenitor cells into mature granulocytes and macrophages (Fleischmann et al, 1986). There is evidence that CSFs stimulate the phagocytic and cytocidal activity of macrophages (Handman and Burgess, 1979;Ho et al, 1990) and promote monocyte and neutrophil antibody-dependent cellular cytotoxicity (Kushner and Cheung, 1989;Liesveld et al, 1991). They may also play a major role in the maturation of dendritic cells into potent activators of resting T cells (Morrissey et al, 1987).…”

mentioning

confidence: 99%

Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

Calatayud¹,

Warner

Mitchell³

2002

Br J Cancer

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Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1b and TNF-a). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their antineoplasic action.

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Cytokine effects and role of adhesive proteins and Fc receptors in human macrophage‐mediated antibody dependent cellular cytotoxicity

Cited by 29 publications

References 32 publications

The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas

The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas

Differential Effect of Cytokine Treatment on Fcα Receptor I- and Fcγ Receptor I-Mediated Tumor Cytotoxicity by Monocyte-Derived Macrophages

Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

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