The High-Affinity IgG Receptor, FcγRI, Plays a Central Role in Antibody Therapy of Experimental Melanoma

Bevaart, Lisette; Jansen, M.; Vugt, Martine J. van; Verbeek, J. Sjef; Winkel, Jan G. J. van de; Leusen, Jeanette H.W.

doi:10.1158/0008-5472.can-05-2856

Cited by 96 publications

(101 citation statements)

References 20 publications

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“…The similar specific binding activity of the mAb P and mAb M BR55-2 to CD64 (FC␥RI) assumes importance because CD64 interaction with Fc of the mAb is essential for IgG-dependent phagocytic and ADCC activities (23)(24)(25). Moreover, it is known that Fc␥RI is the essential receptor for antibody therapy in a mouse melanoma model (26).…”

Section: Discussionmentioning

confidence: 99%

Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells

Brodzik

Glogowska²,

Bandurska³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Although current demands for therapeutic mAbs are growing quickly, production methods to date, including in vitro mammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here we describe the production of mAb BR55-2 (IgG2a) in transgenic plants that recognizes the nonprotein tumor-associated antigen Lewis Y oligosaccharide overexpressed in human carcinomas, particularly breast and colorectal cancers. Heavy and light chains of mAb BR55-2 were expressed separately and assembled in plant cells of low-alkaloid tobacco transgenic plants (Nicotiana tabacum cv. LAMD609). Expression levels of plant-derived mAb (mAb P ) were high (30 mg͞kg of fresh leaves) in T 1 generation plants. Like the mammalian-derived mAb M , the plant mAb P bound specifically to both SK-BR3 breast cancer cells and SW948 colorectal cancer cells. The Fc domain of both mAb P and mAb M showed the similar binding to Fc␥RI receptor (CD64). Comparable levels of cytotoxicity against SK-BR3 cells were also shown for both mAbs in antibody-dependent cell-mediated cytotoxicity assay. Furthermore, plant-derived BR55-2 efficiently inhibited SW948 tumor growth xenografted in nude mice. Altogether, these findings suggest that mAb P originating from low-alkaloid tobacco exhibit biological activities suitable for efficient immunotherapy.breast and colorectal cancer ͉ plant biotechnology ͉ transgenic low-alkaloid tobacco ͉ tumor growth inhibition

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Section: Discussionmentioning

confidence: 99%

Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells

Brodzik

Glogowska²,

Bandurska³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…It has previously been shown that IFN␥ could increase the expression of Fc␥RI in AML cells, which led at one point to the exploration of IFN␥ treatment combined with drug-conjugated anti-Fc␥RI antibody as a potential therapy for AML (17). However, Fc␥RI is not only a candidate therapeutic target; it is also a major effector of phagocytosis in myeloid cells (16,18,19). Hence, we tested the possibility that IFN␥ treatment not only would increase Fc␥RI expression, but would also enhance the phagocytic ability of AML cells.…”

Section: Ifn␥ Increases Fc␥ri Expression and Phagocytic Ability Inmentioning

confidence: 99%

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Fatehchand¹,

McMichael²,

Reader³

et al. 2016

Journal of Biological Chemistry

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Edited by Peter CresswellAcute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFN␥ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFN␥ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of Fc␥RI, which mediates effector responses to therapeutic antibodies. Importantly, IFN␥ was able to up-regulate CD38, the target of the therapeutic antibody daratumumab. Because the antigen (CD38) and effector receptor (Fc␥RI) were both simultaneously up-regulated on the AML blasts, we tested whether IFN␥ treatment of the AML cell lines THP-1 and MV4-11 could stimulate them to target one another after the addition of daratumumab. Results showed that IFN␥ significantly increased daratumumab-mediated cytotoxicity, as measured both by 51 Cr release and lactate dehydrogenase release assays. We also found that the combination of IFN␥ and activation of Fc␥R led to the release of granzyme B by AML cells. Finally, using a murine NSG model of subcutaneous AML, we found that treatment with IFN␥ plus daratumumab significantly attenuated tumor growth. Taken together, these studies show a novel mechanism of daratumumab-mediated killing and a possible new therapeutic strategy for AML.

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“…Antibody-dependent killing of tumor cells by neutrophils in the absence of G-CSF is described to be nonexistent or weak (16,17) and is likely mediated through FcgRIIa (18). Therefore, specific targeting of FcgRI has been proposed, as this may overcome potential inhibitory signals through FcgRIIb when IgG mAbs are employed (19).…”

Section: Most Clinically Used Mabs Belong To the Igg Subclass And Thementioning

confidence: 99%

Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies

Cornet

Mathé

Chettab

et al. 2016

Molecular Cancer Therapeutics

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Therapeutic mAbs exert antitumor activity through various mechanisms, including apoptotic signalization, complementdependent cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP). G-CSF and GM-CSF have been reported to increase the activity of antibodies in preclinical models and in clinical trials. To determine the potential role of pegfilgrastim as an enhancer of anticancer antibodies, we performed a comparative study of filgrastim and pegfilgrastim. We found that pegfilgrastim was significantly more potent than filgrastim in murine xenograft models treated with mAbs. This was observed with rituximab in CD20 þ models and with trastuzumab in HER2 þ models. Stimulation with pegfilgrastim was associated with significant enhancement of leukocyte content in spleen as well as mobilization of activated monocytes/ granulocytes from the spleen to the tumor bed. These results suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mAbs possessing ADCC/ADCP properties.

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The High-Affinity IgG Receptor, FcγRI, Plays a Central Role in Antibody Therapy of Experimental Melanoma

Cited by 96 publications

References 20 publications

Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells

Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies

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