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    Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling

    Lajaunias, Frédéric, Dayer, Jean-Michel, Chizzolini, Carlo
    European Journal of Immunology, 2005, 35, 1, 243-51
    2005
    Disponible
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    Titre: Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling
    Auteur: Lajaunias, Frédéric; Dayer, Jean-Michel; Chizzolini, Carlo
    Date: 2005
    Sujet: Antibodies, Monoclonal/administration & dosage - Antigens, CD/genetics/metabolism - Antigens, Differentiation, Myelomonocytic/genetics/metabolism - Gene Silencing - Humans - Immunity, Innate - Inflammation/etiology/immunology/metabolism - Interleukin-1/biosynthesis - Interleukin-8/biosynthesis - Monocytes/immunology/metabolism - N-Acetylneuraminic Acid/metabolism - Phosphatidylinositol 3-Kinases/metabolism - Sialic Acid Binding Ig-like Lectin 3 - Signal Transduction - Tumor Necrosis Factor-alpha/biosynthesis - P38 Mitogen-Activated Protein Kinases/metabolism
    Description: Human CD33 is a myeloid-restricted transmembrane protein of the sialic acid-binding Ig-like lectin (Siglec) family. While structural analysis predicts an inhibitory function, it remains unknown under which circumstances CD33 may operate as an inhibitory molecule. Here we show that treatment of human monocytes with anti-CD33 mAb induces the production of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-8. However, decreased CD33 surface expression obtained by RNA interference using cognate small interfering RNA (siRNA) was specifically paralleled by spontaneous cytokine production. Similarly, sialic acid (CD33 ligand) removal from the monocyte surface by neuraminidase resulted in IL-1 beta up-regulation, while the addition of red blood cells or sialyllactosamine (but not lactosamine) reversed the effect of neuraminidase treatment, thus demonstrating the importance of ligand recognition by CD33 for repression of monocyte activation. Finally, inhibition of phosphoinositide 3-kinase (PI3K) dramatically enhanced the IL-1 beta response to anti-CD33 and neuraminidase, while inhibition of p38 mitogen-activated protein kinase (MAPK) abolished it. Simultaneous addition of both inhibitors resulted in low levels of IL-1 beta, suggesting that CD33 exerts an inhibitory role mediated by PI3K, while p38 MAPK signaling is required for IL-1 beta production. These data indicate that by controlling monocyte activation, CD33 is a key molecule in the inflammatory response, depending on the sialic acid microenvironment for its repressor activity.
    Fait partie de: European Journal of Immunology, 2005, 35, 1, 243-51

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    Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154

    Molano, R Damaris, Pileggi, Antonello, Berney, Thierry, Poggioli, Raffaella, Zahr, Elsie, Oliver, Robert, Ricordi, Camillo, Rothstein, David M, Basadonna, Giacomo P, Inverardi, Luca
    Diabetes, 2003, 52, 4, 957-64
    2003
    Disponible
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    Titre: Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154
    Auteur: Molano, R Damaris; Pileggi, Antonello; Berney, Thierry; Poggioli, Raffaella; Zahr, Elsie; Oliver, Robert; Ricordi, Camillo; Rothstein, David M; Basadonna, Giacomo P; Inverardi, Luca
    Date: 2003
    Sujet: Animals - Antibodies, Monoclonal/administration & dosage - Antigens, CD3/immunology - Antigens, CD45/immunology - CD40 Ligand/immunology - CD8-Positive T-Lymphocytes/immunology - Female - Graft Survival - Interferon-gamma/biosynthesis/genetics - Interleukin-10/genetics - Interleukin-2/genetics - Interleukin-7/pharmacology - Islets of Langerhans Transplantation - Lymphocyte Activation - Mice - Mice, Inbred NOD - RNA, Messenger/analysis - Transplantation, Homologous
    Description: Clinical islet transplantation is a successful procedure that can improve the quality of life in recipients with diabetes. A drawback of the procedure is the need for chronic administration of immunosuppressive drugs that, among other side effects, are potentially diabetogenic. Definition of immunosuppressive protocols that utilize nondiabetogenic compounds could further improve islet transplantation outcome. We used the NOD mouse to assess the effect of targeting the T-lymphocyte surface receptors CD45RB and CD154 in preventing loss of allogeneic islet grafts as a result of recurrence of autoimmunity and allorejection. Administration of the two antibodies led to significantly prolonged allograft survival, with a percentage of grafts surviving long-term. The therapeutic efficacy of the treatment was paralleled by a shift in CD45RB isoform expression on T-lymphocytes, increased in vitro responsiveness to interleukin-7, and increased in vitro gamma-interferon production after anti-CD3 antibody stimulation. Furthermore, graft infiltration by CD8+ T-cells was remarkably reduced. Recipient mice bearing functioning allografts were otherwise immunocompetent, as assessed in vivo and in vitro by numerous tests, including intragraft cytokine production, responsiveness to polyclonal stimulation and alloantigens, and analysis of cell subset phenotype. These data show that nondiabetogenic regimens of immunomodulation can lead to prolonged islet allograft survival in the challenging NOD mouse model.
    Fait partie de: Diabetes, 2003, 52, 4, 957-64

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    Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors

    Gordon, Michael S, Sweeney, Christopher S, Mendelson, David S, Eckhardt, S Gail, Anderson, Abraham, Beaupre, Darrin M, Branstetter, Daniel, Burgess, Teresa L, Coxon, Angela, Deng, Hongjie, Kaplan-Lefko, Paula, Leitch, Ian M, Oliner, Kelly S, Yan, Lucy, Zhu, Min, Gore, Lia
    Clinical cancer research : an official journal of the American Association for Cancer Research, 15 January 2010, Vol.16(2), pp.699-710 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors
    Auteur: Gordon, Michael S; Sweeney, Christopher S; Mendelson, David S; Eckhardt, S Gail; Anderson, Abraham; Beaupre, Darrin M; Branstetter, Daniel; Burgess, Teresa L; Coxon, Angela; Deng, Hongjie; Kaplan-Lefko, Paula; Leitch, Ian M; Oliner, Kelly S; Yan, Lucy; Zhu, Min; Gore, Lia
    Sujet: Antibodies, Monoclonal -- Administration & Dosage ; Neoplasms -- Drug Therapy
    Description: The aims were to assess the safety, pharmacokinetics, maximum tolerated dose, and antitumor activity of AMG 102, a fully human hepatocyte growth factor/scatter factor (HGF/SF)-neutralizing monoclonal antibody, in patients with solid tumors. Patients (N = 40) with refractory advanced solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 mg/kg AMG 102 every 2 weeks). Safety, anti-AMG 102 antibody formation, pharmacokinetics, tumor response, and exploratory biomarkers were assessed. AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, and the maximum tolerated dose was not reached. Treatment-related adverse events were generally mild and included fatigue (13%), constipation (8%), nausea (8%), vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced grade 3 upper gastrointestinal hemorrhage. No anti-AMG 102 antibodies were detected, and AMG 102 had linear pharmacokinetics within the dose range investigated. Sixteen of 23 (70%) evaluable patients had a best response of stable disease with progression-free survival ranging from 7.9 to 40 weeks. Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a dose-dependent manner, whereas soluble c-Met concentrations were generally similar across doses. AMG 102 is safe and well tolerated, has a favorable pharmacokinetic profile, and will be further investigated as a monotherapy and in combination with other agents.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 January 2010, Vol.16(2), pp.699-710
    Identifiant: 1078-0432 (ISSN); 20068101 Version (PMID); 10.1158/1078-0432.CCR-09-1365 (DOI)

    • Plusieurs versions

    Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials

    Quattrocchi, Emilia, Østergaard, Mikkel, Taylor, Peter C, Van Vollenhoven, Ronald F, Chu, Myron, Mallett, Stephen, Perry, Hayley, Kurrasch, Regina
    PloS one, 2016, Vol.11(6), pp.e0157961 [Revue évaluée par les pairs]

    • Plusieurs versions

    The anti-(+)-methamphetamine monoclonal antibody mAb7F9 attenuates acute (+)-methamphetamine effects on intracranial self-stimulation in rats

    Harris, Andrew C, Lesage, Mark G, Shelley, David, Perry, Jennifer L, Pentel, Paul R, Owens, S Michael
    PloS one, 2015, Vol.10(3), pp.e0118787 [Revue évaluée par les pairs]

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    FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma

    Chuk, Meredith K, Chang, Jennie T, Theoret, Marc R, Sampene, Emmanuel, He, Kun, Weis, Shawna L, Helms, Whitney S, Jin, Runyan, Li, Hongshan, Yu, Jingyu, Zhao, Hong, Zhao, Liang, Paciga, Mark, Schmiel, Deborah, Rawat, Rashmi, Keegan, Patricia, Pazdur, Richard
    Clinical cancer research : an official journal of the American Association for Cancer Research, 01 October 2017, Vol.23(19), pp.5666-5670 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma
    Auteur: Chuk, Meredith K; Chang, Jennie T; Theoret, Marc R; Sampene, Emmanuel; He, Kun; Weis, Shawna L; Helms, Whitney S; Jin, Runyan; Li, Hongshan; Yu, Jingyu; Zhao, Hong; Zhao, Liang; Paciga, Mark; Schmiel, Deborah; Rawat, Rashmi; Keegan, Patricia; Pazdur, Richard
    Sujet: Antibodies, Monoclonal -- Administration & Dosage ; Antibodies, Monoclonal, Humanized -- Administration & Dosage ; Melanoma -- Drug Therapy
    Description: On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders....
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 October 2017, Vol.23(19), pp.5666-5670
    Identifiant: 1078-0432 (ISSN); 28235882 Version (PMID); 10.1158/1078-0432.CCR-16-0663 (DOI)

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    A phase I first-in-human study of TRC105 (Anti-Endoglin Antibody) in patients with advanced cancer

    Rosen, Lee S, Hurwitz, Herbert I, Wong, Michael K, Goldman, Jonathan, Mendelson, David S, Figg, William D, Spencer, Shawn, Adams, Bonne J, Alvarez, Delia, Seon, Ben K, Theuer, Charles P, Leigh, Bryan R, Gordon, Michael S
    Clinical cancer research : an official journal of the American Association for Cancer Research, 01 September 2012, Vol.18(17), pp.4820-9 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: A phase I first-in-human study of TRC105 (Anti-Endoglin Antibody) in patients with advanced cancer
    Auteur: Rosen, Lee S; Hurwitz, Herbert I; Wong, Michael K; Goldman, Jonathan; Mendelson, David S; Figg, William D; Spencer, Shawn; Adams, Bonne J; Alvarez, Delia; Seon, Ben K; Theuer, Charles P; Leigh, Bryan R; Gordon, Michael S
    Sujet: Antigens, CD ; Receptors, Cell Surface ; Antibodies, Monoclonal -- Administration & Dosage ; Neoplasms -- Drug Therapy
    Description: TRC105 is a chimeric IgG1 monoclonal antibody that binds CD105 (endoglin). This first-in-human, phase I, open-label study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in patients with advanced refractory solid tumors. Patients received escalating doses of intravenous TRC105 until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design. Fifty patients were treated with escalating doses of TRC105. The maximum tolerated dose (MTD) was exceeded at 15 mg/kg every week because of dose-limiting hypoproliferative anemia. TRC105 exposure increased with increasing dose, and continuous serum concentrations that saturate CD105 receptors were maintained at 10 mg/kg weekly (the MTD) and 15 mg/kg every 2 weeks. Common adverse events including anemia, telangiectasias, and infusion reactions reflected the mechanism of action of the drug. Antibodies to TRC105 were not detected in patients treated with TRC105 from Chinese hamster ovary cells being used in ongoing phase Ib and phase II studies. Stable disease or better was achieved in 21 of 45 evaluable patients (47%), including two ongoing responses at 48 and 18 months. TRC105 was tolerated at 10 mg/kg every week and 15 mg/kg every 2 weeks, with a safety profile that was distinct from that of VEGF inhibitors. Evidence of clinical activity was seen in a refractory patient population. Ongoing clinical trials are testing TRC105 in combination with chemotherapy and VEGF inhibitors and as a single agent in prostate, ovarian, bladder, breast, and hepatocellular cancer.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 September 2012, Vol.18(17), pp.4820-9
    Identifiant: 1078-0432 (ISSN); 22767667 Version (PMID); 10.1158/1078-0432.CCR-12-0098 (DOI)

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    Phase I dose-escalation study of onartuzumab as a single agent and in combination with bevacizumab in patients with advanced solid malignancies

    Salgia, Ravi, Patel, Premal, Bothos, John, Yu, Wei, Eppler, Steve, Hegde, Priti, Bai, Shuang, Kaur, Surinder, Nijem, Ihsan, Catenacci, Daniel V T, Peterson, Amy, Ratain, Mark J, Polite, Blase, Mehnert, Janice M, Moss, Rebecca A
    Clinical cancer research : an official journal of the American Association for Cancer Research, 15 March 2014, Vol.20(6), pp.1666-75 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: Phase I dose-escalation study of onartuzumab as a single agent and in combination with bevacizumab in patients with advanced solid malignancies
    Auteur: Salgia, Ravi; Patel, Premal; Bothos, John; Yu, Wei; Eppler, Steve; Hegde, Priti; Bai, Shuang; Kaur, Surinder; Nijem, Ihsan; Catenacci, Daniel V T; Peterson, Amy; Ratain, Mark J; Polite, Blase; Mehnert, Janice M; Moss, Rebecca A
    Sujet: Antibodies, Monoclonal -- Administration & Dosage ; Antineoplastic Agents -- Administration & Dosage ; Neoplasms -- Drug Therapy
    Description: This first-in-human study evaluated the safety, immunogenicity, pharmacokinetics, and antitumor activity of onartuzumab, a monovalent antibody against the receptor tyrosine kinase MET. This 3+3 dose-escalation study comprised three stages: (i) phase Ia dose escalation of onartuzumab at doses of 1, 4, 10, 20, and 30 mg/kg intravenously every 3 weeks; (ii) phase Ia cohort expansion at the recommended phase II dose (RP2D) of 15 mg/kg; and (iii) phase Ib dose escalation of onartuzumab at 10 and 15 mg/kg in combination with bevacizumab (15 mg/kg intravenously every 3 weeks). Serum samples were collected for evaluation of pharmacokinetics, potential pharmacodynamic markers, and antitherapeutic antibodies. Thirty-four patients with solid tumors were treated in phase Ia and 9 in phase Ib. Onartuzumab was generally well tolerated at all dose levels evaluated; the maximum tolerated dose was not reached. The most frequent drug-related adverse events included fatigue, peripheral edema, nausea, and hypoalbuminemia. In the phase Ib cohort, onartuzumab at the RP2D was combined with bevacizumab and no dose-limiting toxicities were seen. Onartuzumab showed linear pharmacokinetics in the dose range from 4 to 30 mg/kg. The half-life was approximately 8 to 12 days. There were no apparent pharmacokinetic interactions between onartuzumab and bevacizumab, and antitherapeutic antibodies did not seem to affect the safety or pharmacokinetics of onartuzumab. A patient with gastric carcinoma in the 20-mg/kg dose cohort achieved a durable complete response for nearly 2 years. Onartuzumab was generally well tolerated as a single agent and in combination with bevacizumab in patients with solid tumors.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 March 2014, Vol.20(6), pp.1666-75
    Identifiant: 1078-0432 (ISSN); 24493831 Version (PMID); 10.1158/1078-0432.CCR-13-2070 (DOI)

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    Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies

    Dai, Min, Yip, Yuen Yee, Hellstrom, Ingegerd, Hellstrom, Karl Erik
    Clinical cancer research : an official journal of the American Association for Cancer Research, 01 March 2015, Vol.21(5), pp.1127-38 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies
    Auteur: Dai, Min; Yip, Yuen Yee; Hellstrom, Ingegerd; Hellstrom, Karl Erik
    Sujet: Antibodies, Monoclonal -- Administration & Dosage ; Immunologic Factors -- Administration & Dosage ; Neoplasms -- Immunology
    Description: Immunomodulatory mAbs can treat cancer, but cures are rare except for small tumors. Our objective was to explore whether the therapeutic window increases by combining mAbs with different modes of action and injecting them into tumors. Combinations of mAbs to CD137/PD-1/CTLA-4 or CD137/PD-1/CTLA-4/CD19 were administrated intratumorally to mice with syngeneic tumors (B16 and SW1 melanoma, TC1 lung carcinoma), including tumors with a mean surface of approximately 80 mm(2). Survival and tumor growth were assessed. Immunologic responses were evaluated using flow cytometry and qRT-PCR. More than 50% of tumor-bearing mice had complete regression and long-term survival after tumor injection with mAbs recognizing CD137/PD-1/CTLA-4/CD19 with similar responses in three models. Intratumoral injection was more efficacious than intraperitoneal injection in causing rejection also of untreated tumors in the same mice. The three-mAb combination could also induce regression, but was less efficacious. There were few side effects, and therapy-resistant tumors were not observed. Transplanted tumor cells rapidly caused a Th2 response with increased CD19 cells. Successful therapy shifted this response to the Th1 phenotype with decreased CD19 cells and increased numbers of long-term memory CD8 effector cells and T cells making IFNγ and TNFα. Intratumoral injection of mAbs recognizing CD137/PD-1/CTLA-4/CD19 can eradicate established tumors and reverse a Th2 response with tumor-associated CD19 cells to Th1 immunity, whereas a combination lacking anti-CD19 is less effective. There are several human cancers for which a similar approach may provide clinical benefit.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 March 2015, Vol.21(5), pp.1127-38
    Identifiant: 1078-0432 (ISSN); 25142145 Version (PMID); 10.1158/1078-0432.CCR-14-1339 (DOI)

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    Monoclonal antibody against the ectodomain of E-cadherin (DECMA-1) suppresses breast carcinogenesis: involvement of the HER/PI3K/Akt/mTOR and IAP pathways

    Brouxhon, Sabine M, Kyrkanides, Stephanos, Teng, Xiaofei, Raja, Veena, O'Banion, M Kerry, Clarke, Robert, Byers, Stephen, Silberfeld, Andrew, Tornos, Carmen, Ma, Li
    Clinical cancer research : an official journal of the American Association for Cancer Research, 15 June 2013, Vol.19(12), pp.3234-46 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: Monoclonal antibody against the ectodomain of E-cadherin (DECMA-1) suppresses breast carcinogenesis: involvement of the HER/PI3K/Akt/mTOR and IAP pathways
    Auteur: Brouxhon, Sabine M; Kyrkanides, Stephanos; Teng, Xiaofei; Raja, Veena; O'Banion, M Kerry; Clarke, Robert; Byers, Stephen; Silberfeld, Andrew; Tornos, Carmen; Ma, Li
    Sujet: Antibodies, Monoclonal -- Administration & Dosage ; Breast Neoplasms -- Therapy ; Cadherins -- Immunology ; Carcinogenesis -- Drug Effects
    Description: Although targeted therapies against HER2 have been one of the most successful therapeutic strategies for breast cancer, patients eventually developed acquired resistance from compensatory upregulation of alternate HERs and mitogen-activated protein kinase-phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling. As we and others have shown that the soluble ectodomain fragment of E-cadherin exerts prooncogenic effects via HER1/2-mediated binding and activation of downstream prosurvival pathways, we explored whether targeting this ectodomain [DECMA-1 monoclonal antibody (mAb)] was effective in the treatment of HER2-positive (HER2(+)) breast cancers. MMTV-PyMT transgenic mice and HER2(+)/E-cadherin-positive MCF-7 and BT474 trastuzumab-resistant (TtzmR) cells were treated with the DECMA-1 mAb. Antitumor responses were assessed by bromodeoxyuridine incorporation, apoptosis, and necrosis. The underlying intracellular prooncogenic pathways were explored using subcellular fractionation, immunoprecipitation, fluorescence microscopy, and immunoblotting. Treatment with DECMA-1 mAb significantly delayed tumor onset and attenuated tumor burden in MMTV-PyMT mice by reducing tumor cell proliferation and inducing apoptosis without any detectable cytotoxicity to mice or end-organs. In vitro treatment of MCF-7 and BT474 TtzmR cells reduced proliferation and induced cancer cell apoptosis. Importantly, this inhibition of breast tumorigenesis was due to concomitant downregulation, via ubiquitin-mediated degradation through the lysosome and proteasome pathways, of all HER family members, components of downstream PI3K/Akt/mTOR prosurvival signaling and suppression of inhibitor of apoptosis proteins. Our results establish that the E-cadherin ectodomain-specific mAb DECMA-1 inhibits Ecad(+)/HER2(+) breast cancers by hindering tumor growth and inducing apoptosis via downregulation of key oncogenic pathways involved in trastuzumab resistance, thereby establishing a novel therapeutic platform for the treatment of HER2(+) breast cancers.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 June 2013, Vol.19(12), pp.3234-46
    Identifiant: 1078-0432 (ISSN); 23620408 Version (PMID); 10.1158/1078-0432.CCR-12-2747 (DOI)