Direct killing of interleukin-2-transfected tumor cells by human neutrophils

Pericle, Federica; Kirken, Robert A.; Epling-Burnette, Pearlie K.; Blanchard, D K; Djeu, Julie Y.

doi:10.1002/(sici)1097-0215(19960503)66:3<367::aid-ijc17>3.0.co;2-8

Cited by 30 publications

(18 citation statements)

References 33 publications

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“…9-11). Neutrophils have been described as potent cytotoxic effectors, able to produce many cytotoxic molecules (12) and exert direct tumoricidal activity (13). Their ability to directly recognize tumor cells is limited but is highly enhanced in the presence of mAbs (14).…”

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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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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“…One group found that the levels of Stat5a, Stat5b, and Stat1 were all decreased in puri®ed T cells isolated from HIV patients, suggesting that the reduction of these STAT proteins may contribute to the loss of T cell function over the course of HIV infection (Pericle et al, 1998). In contrast, an independent study showed that the C-terminal truncated Stat5 and Stat1a were constitutively activated in peripheral blood mononuclear cells isolated from HIV patients (Bovolenta et al, 1999).…”

Section: Potential Roles Of Stat5 In Transformation Immune Surveillamentioning

confidence: 99%

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

2000

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Section: Discussionmentioning

confidence: 99%

“…In the former model, moreover, the extent and rapidity of neutrophil recruitment is proportional to the amount of IL-2 released from the transduced cells. IL-2 may recruit and activate PMN cells either directly through the interaction with its receptor (Djeu et al, 1993;Liu et al, 1994), leading to cytokine secretion and stimulation of tumoricidal activity (Wei et al, 1993(Wei et al, , 1994Girard et al, 1995;Pericle et al, 1996), or through its action on T-and NK cells, leading to a cascade of secondary neutrophil-activating cytokines and chemokines, such as IL-8 and TNF-α.The subsequent complete rejection of EJ-IL-2 cells by PMNdepleted and irradiated nu/nu mice suggests the emergence of alternative effector mechanisms, mediated by NK cells and monocyte/macrophages. Both NK cells and monocyte/macrophages have indeed been implicated in the rejection of IL-2-secreting cancer cells by mice lacking functional T-and B-cells (Alosco et al, 1993;Hara et al, 1995).…”

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confidence: 99%

Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder

et al. 1999

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Summary Transitional cell carcinoma of the bladder is one of the human cancers most responsive to immunotherapy, and local interleukin-2 (IL-2) production appears to be an important requirement for immunotherapy to be effective. In this study, we engineered two human bladder cancer cell lines (RT112 and EJ) to constitutively release human IL-2 by retroviral vector-mediated gene transfer. Following infection and selection, stable and consistent production of biologically active IL-2 was demonstrated at both the mRNA and the protein level. Morphology, in vitro growth rate and proliferation, as well as other cytokine gene mRNA or membrane adhesion receptor expression, were not altered in IL-2 transduced cells as compared to their parental or control vector-infected counterparts. Moreover, IL-2 engineered cells lost their tumorigenicity into nu/nu mice and the mechanism of rejection appeared to involve multiple host effector cell populations, among which a prominent role was played by neutrophils and radiosensitive cells. These findings may offer support to the development of an IL-2-based gene therapy approach to human bladder cancer.Keywords: human; interleukin-2; transitional bladder cancer; gene therapy; immunotherapy 770British Journal of Cancer (1999) 79(5/6), 770-779 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 17 November 1997 Revised 16 April 1998 Accepted 28 May 1998 Correspondence to: A Santoni MATERIALS AND METHODS Cell linesThe human transitional bladder carcinoma cell lines RT112 and EJ (also known as MGH-U1) were kindly provided by Dr Prescott (Department of Surgery/Urology, Western General Hospital, Edinburgh, UK). Both cell lines were cultured in Roswell Park Memorial Institute (RPMI)-1640 medium (Gibco, Paisley, UK) supplemented with 10% fetal calf serum (FCS, Gibco), 50 U/ml penicillin, 50 µg/ml streptomycin and 2 mM glutamine (Flow Laboratories, Irvine, UK). IL-2 gene transductionIL-2 cDNA cloned from human peripheral blood lymphocytes was inserted into the Moloney murine leukaemia virus-derived retroviral vector LXSN containing the selectable marker NeoR, and producer cells were obtained by transfection as previously described (Dusty Miller and Rosman, 1989;Melani et al, 1994). RT112 or EJ cells (10 6 ) were exposed to undiluted viral supernatant for 3 h in the presence of 8 µg ml -1 of polybrene, and selected in 0.8 mg ml -1 G418 (Sigma Chemical Co., St Louis, MO, USA). RT112 or EJ cells infected with the LXSN vector were used as a transfection control in all experiments. Proliferation assayFive thousand cells/well were seeded in flat bottom 96-well microplates and cultured in triplicates under different conditions (see Figure 2). Cells were labelled with 74 kBq of [ 3 H]TdR (methyl-3 H-thymidine, 185 GBq mmol, 5 Ci mmol -1 , Amersham Life Sciences, Milano, Italy)/well, harvested 18 h later, and [ 3 H]TdR uptake was determined by liquid scintillation spectrometry and expressed as total counts per minute (cpm).To measure released IL-2 biological activity, 2.5 × 10 5 infect...

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Direct killing of interleukin-2-transfected tumor cells by human neutrophils

Cited by 30 publications

References 33 publications

Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies

Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder

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