Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

Mineo, J.-F.; Bordron, Anne; Quintin-Roué, Isabelle; Loisel, Séverine; Ster, KL; Buhé, Virginie; Lagarde, N; Berthou, Christian

doi:10.1038/sj.bjc.6602089

Cited by 52 publications

(35 citation statements)

References 22 publications

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“…3E through I), in 51 Cr release assay, suggest that the degree of cytotoxicity of trastuzumab against MRT cells depends on their level of HER-2 expression. The ADCC effect of trastuzumab was also highly correlated with HER-2 expression in other cancer cells (9,32,40). Moreover, using autologous human PBMC of the patient from which the cell line had been established, the cytotoxicity was also significantly enhanced by trastuzumab against the KP-MRT-YM cell line (Fig.…”

Section: Discussionmentioning

confidence: 80%

Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity

Katsumi

Kuwahara²,

Tamura³

et al. 2008

Clinical Cancer Research

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Purpose: Malignant rhabdoid tumor (MRT) is an early childhood cancer with poor prognosis.Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), has been shown to be effective against breast cancer and other cancers.We investigated the effect of trastuzumab on MRTcell lines. Experimental Design: We examined expression of HER-2 on four MRTcell lines and two tumor tissues by indirect immunofluorescence, flow cytometry, and immunohistochemistry. The effect of trastuzumab against MRT cells was examined by cell growth assay. To observe the antibodydependent cellular cytotoxicity of effector cells, we examined the cytotoxicity of trastuzumab in combination with allogeneic or autologous human peripheral blood mononuclear cells with and without IL-2 using the chromium release assay. Results: All four MRT cell lines and both MRT tissues expressed HER-2 protein. Trastuzumab alone did not reduce the viability of the MRT cell lines. On the other hand, the cytotoxicity of trastuzumab against each of the MRT cell lines was significantly increased by the presence of allogeneic and autologous peripheral blood mononuclear cells (P < 0.01). There was a strong correlation coefficient (r = 0.825) between HER-2 expression and the cytotoxicity enhanced by trastuzumab. Moreover, trastuzumab in combination with peripheral blood mononuclear cells augmented by interleukin-2 (IL-2) was significantly more cytotoxic than trastuzumab alone or IL-2 alone (P < 0.01). Conclusions:Our results indicate that (1) trastuzumab can exert antitumor effects on MRTcells by using the antibody-dependent cellular cytotoxicity of effector cells and (2) IL-2 can enhance the cytotoxicity of trastuzumab against MRTcells.Malignant rhabdoid tumor (MRT) is a highly aggressive malignancy of early childhood. The most common locations are in the central nervous system and kidney, although such tumors may arise in almost any site (1). In the past several years, there has been significant progress in the genetic studies, which indicated that the majority of MRT harbor biallelic inactivation in the integrase interactor 1 (INI1) tumor suppressor gene, located in chromosome 22q11.2 (2). However, the overall survival rate of patients with MRT of the kidney is not more than 20% to 25%. For example, only 8.8% of infants that were diagnosed before the age of 6 months were living 4 years after diagnosis (3). Therefore, the search for effective treatments against MRT is needed.Human epidermal growth factor receptor type 2 (HER-2) belongs to the epidermal growth factor receptor (EGFR) family. HER-2 can mediate signal transduction from all EGFR family and is thus involved in a variety of cell functions, including cell proliferation, differentiation, and apoptosis. In addition, HER-2 also plays a pivotal role in oncogenic transformation and tumorigenesis (4 -8). Overexpression and amplification of HER-2 has been identified in a variety of cancer types, including non-small cell lung cancer and carcinomas of the breast, bladder...

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Section: Discussionmentioning

confidence: 80%

Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity

Katsumi

Kuwahara²,

Tamura³

et al. 2008

Clinical Cancer Research

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“…Such molecular targets would minimize toxic effects on surrounding normal tissue. The epidermal growth factor receptor (Barth et al, 2002), platelet derived growth factor receptor (Hermanson et al, 1992), fibroblast growth factor receptor (Morrison et al, 1994), human epidermal receptor type 2 (Mineo et al, 2004), and interleukin-13 receptor (Mintz et al, 2002) have been shown to be upregulated in glioma cells. We have previously shown that human GBM cell lines express high levels of LDL receptors (Maletinska et al, 2000) and demonstrated that boronated protoporphryn is delivered to the SF-767 GBM cell line by LDL (Callahan et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

Nikanjam

Blakely

Bjornstad

et al. 2007

International Journal of Pharmaceutics

108

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The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed and tested to determine its utility as a drug Collectively these data strongly suggest that the synthetic nano-LDLs described here are taken up by LDLR and can serve as a drug delivery vehicle for targeting GBM tumors via the LDLR.3

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“…Proof of principle for this application is seen with Herceptin, an anti-HER2 antibody, effective in the treatment of some breast cancer patients with systemic disease (i.e., not involving CNS) whose tumors overexpress this receptor. Herceptin has been shown to mediate cell death of HER2/neu -expressing glioblastoma cell lines in vitro, but in vivo activity against intra-CNS tumors is lacking, perhaps due to impaired uptake in the CNS (56). These include unmodified and modified antibodies, targeted against EGFRvIII.…”

Section: The Egfr Family and Targeted Therapies In Malignant Gliomamentioning

confidence: 99%

Epidermal Growth Factor Receptor–Mediated Signal Transduction in the Development and Therapy of Gliomas

Nicholas

Lukas²,

Jafri

et al. 2006

Clinical Cancer Research

195

131

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The epidermal growth factor receptor (EGFR) and its ligands figure prominently in the biology of gliomas, the most common tumors of the central nervous system (CNS). Although their histologic classification seems to be straightforward, these tumors constitute a heterogeneous class of related neoplasms. They are associated with a variety of molecular abnormalities affecting signal transduction, transcription factors, apoptosis, angiogensesis, and the extracellular matrix. Under normal conditions, these same interacting factors drive CNS growth and development. We are now recognizing the diverse molecular genetic heterogeneity that underlies tumors classified histologically into three distinct grades. This recognition is leading to new therapeutic strategies targeted directly at specific molecular subtypes. In this article, we will review the role of EGFR and related molecular pathways in the genesis of the normal CNS and their relationship to glial tumorigenesis. We will discuss barriers to effective treatment as they relate to anatomic specialization of the CNS. We will also consider the ways in which specific EGFR alterations common to glioma reflect outcomes following treatment with targeted therapies, all with an eye towards applying this understanding to improved patient outcomes. Epidermal growth factor (EGF) was identified by embryologistStanley Cohen in the early 1960s and its receptor (EGFR) was identified a decade later (1, 2). During that time and in the decades that followed, a family of related factors and their receptors were identified. The complex intracellular effects that follow activation of these receptors were subsequently elaborated. Together, this would prove to be of critical importance in our understanding of both normal growth and development and neoplastic transformation. This review will focus on the role of these receptor-ligand interactions in primary brain tumor biology. We will briefly discuss their importance in the development of normal brain and the implication of those roles for tumorigenesis. Following a review of specific abnormalities in brain tumors, we will conclude with a summary of brain tumor therapies that include EGFR-mediated signaling in their rationale. Receptor-Ligand InteractionsThe EGFR was the first of the human EGF receptor (HER) family members to be discovered. The HER family proteins are members of the receptor tyrosine kinase (RTK) superfamily. The platelet-derived growth factor receptor (PDGFR), another RTK family member, is also important in brain tumor biology. The ligands for the HER family receptors are also diverse. They include the EGF family and the structurally related neuregulin family. Both are produced by many cell types, including neurons and glia. All of the ligands function via autocrine and/ or paracrine signaling. The EGF family includes EGF, transforming growth factor-a (TGF-a), heparin-binding EGF, amphiregulin, betacellulin, and epiregulin (3).The neuregulin (NRG) family consists of the protein products derived from the alternat...

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Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

Cited by 52 publications

References 22 publications

Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity

Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity

Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

Epidermal Growth Factor Receptor–Mediated Signal Transduction in the Development and Therapy of Gliomas

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