Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101.

Abstract:

:GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassical induction of apoptosis cytotoxicity, with more direct cytotoxicity and more antibody-dependent cell-mediated cytotoxicity. We evaluated the antitumor activity of GA101 against the human-transformed follicular lymphoma RL model in vivo in severe combined immunodeficient mice (SCID) mice. GA101 induced stronger inhibition of tumor growth than rituximab. Combination of GA101 with cyclophosphamide in vivo confirmed the superiority of GA101 over rituximab. Neutralizing the complement system with cobra venom factor partially impaired the antitumor activity of rituximab, but had no impact on the efficacy of GA101. In vitro GA101 more potently induced cell death of RL cells than rituximab. The expression of a limited number of genes was found to be induced by both antibodies after exposure in vitro. Among these, early growth response 1 and activation transcription factor 3 were confirmed to be increased at the protein level, suggesting a possible role of these proteins in the apoptotic signalling of anti-CD20 antibodies. These data imply that GA101 is superior to rituximab not only as a single agent, but also in combination with chemotherapy. These data suggest the presence of novel signalization pathways activated after exposure to anti-CD20 antibodies.

journal_name

Mol Cancer Ther

authors

Dalle S,Reslan L,Besseyre de Horts T,Herveau S,Herting F,Plesa A,Friess T,Umana P,Klein C,Dumontet C

doi

10.1158/1535-7163.MCT-10-0385

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

178-85

issue

1

eissn

1535-7163

issn

1538-8514

pii

10/1/178

journal_volume

10

pub_type

杂志文章
  • Dual Inhibition of Key Proliferation Signaling Pathways in Triple-Negative Breast Cancer Cells by a Novel Derivative of Taiwanin A.

    abstract::The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, w...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0011

    authors: Kuo YH,Chiang EI,Chao CY,Rodriguez RL,Chou PY,Tsai SY,Pai MH,Tang FY

    更新日期:2017-03-01 00:00:00

  • Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells.

    abstract::Artesunate, the active agent from Artemisia annua L. used in the traditional Chinese medicine, is being applied as a first-line drug for malaria treatment, and trials are ongoing that include this drug in cancer therapy. Despite increasing interest in its therapeutic application, the mode of cell killing provoked by a...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-11-0534

    authors: Berdelle N,Nikolova T,Quiros S,Efferth T,Kaina B

    更新日期:2011-12-01 00:00:00

  • Characterization of the cytotoxic activities of novel analogues of the antitumor agent, lavendamycin.

    abstract::Lavendamycin is a bacterially derived quinolinedione that displays significant antimicrobial and antitumor activities. However, preclinical development of lavendamycin as an anticancer agent was halted due to the poor aqueous solubility and relatively nonspecific cytotoxic activity of this compound. In this report, we...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Fang Y,Linardic CM,Richardson DA,Cai W,Behforouz M,Abraham RT

    更新日期:2003-06-01 00:00:00

  • A bead-based activity screen for small-molecule inhibitors of signal transduction in chronic myelogenous leukemia cells.

    abstract::Chronic myelogenous leukemia is characterized by the presence of the chimeric BCR-ABL gene, which is expressed as the constitutively active Bcr-Abl kinase. Although kinase activity is directly responsible for the clinical phenotype, current diagnostic and prognostic methods focus on a genetic classification system in ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-10-0157

    authors: Sylvester JE,Kron SJ

    更新日期:2010-05-01 00:00:00

  • Novel inhibitors of Rad6 ubiquitin conjugating enzyme: design, synthesis, identification, and functional characterization.

    abstract::Protein ubiquitination is important for cell signaling, DNA repair, and proteasomal degradation, and it is not surprising that alterations in ubiquitination occur frequently in cancer. Ubiquitin-conjugating enzymes (E2) mediate ubiquitination by selective interactions with ubiquitin-activating (E1) and ubiquitin ligas...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-12-0793

    authors: Sanders MA,Brahemi G,Nangia-Makker P,Balan V,Morelli M,Kothayer H,Westwell AD,Shekhar MPV

    更新日期:2013-04-01 00:00:00

  • Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2.

    abstract::The standard treatment for advanced, androgen-responsive prostate cancer is androgen deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually progresses to an androgen-r...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0823

    authors: Feng S,Tang Q,Sun M,Chun JY,Evans CP,Gao AC

    更新日期:2009-03-01 00:00:00

  • Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2.

    abstract::The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to dr...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-14-0669

    authors: Soares HP,Ming M,Mellon M,Young SH,Han L,Sinnet-Smith J,Rozengurt E

    更新日期:2015-04-01 00:00:00

  • Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses NF2 Loss-Driven Tumorigenesis.

    abstract::Inactivation of NF2/Merlin causes the autosomal-dominant cancer predisposition syndrome familial neurofibromatosis type 2 (NF2) and contributes to the development of malignant pleural mesothelioma (MPM). To develop a targeted therapy for NF2-mutant tumors, we have exploited the recent realization that Merlin loss driv...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0821

    authors: Cooper J,Xu Q,Zhou L,Pavlovic M,Ojeda V,Moulick K,de Stanchina E,Poirier JT,Zauderer M,Rudin CM,Karajannis MA,Hanemann CO,Giancotti FG

    更新日期:2017-08-01 00:00:00

  • 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, a specific glutathione S-transferase inhibitor, overcomes the multidrug resistance (MDR)-associated protein 1-mediated MDR in small cell lung cancer.

    abstract::In the present work, we have investigated the antitumor activity of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on aggressive small cell lung cancer. NBDHEX not only is cytotoxic toward the parental small cell lung cancer H69 cell line (LC(50) of 2.3 +/- 0.6 micromol/L) but also overcomes the multidrug re...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-0487

    authors: Filomeni G,Turella P,Dupuis ML,Forini O,Ciriolo MR,Cianfriglia M,Pezzola S,Federici G,Caccuri AM

    更新日期:2008-02-01 00:00:00

  • Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction.

    abstract::NB1011, a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, is a novel small molecule anticancer agent. NB1011 is selectively active against tumor cells expressing high levels of thymidylate synthase (TS), a critical enzyme in DNA biosynthesis. NB1011 is different from the current TS-targeted drugs, ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Neuteboom ST,Karjian PL,Boyer CR,Beryt M,Pegram M,Wahl GM,Shepard HM

    更新日期:2002-04-01 00:00:00

  • Targeting the PI3K/AKT Pathway Overcomes Enzalutamide Resistance by Inhibiting Induction of the Glucocorticoid Receptor.

    abstract::The PI3K-AKT pathway has pleiotropic effects and its inhibition has long been of interest in the management of prostate cancer, where a compensatory increase in PI3K signaling has been reported following androgen receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction of other hormo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-19-0936

    authors: Adelaiye-Ogala R,Gryder BE,Nguyen YTM,Alilin AN,Grayson AR,Bajwa W,Jansson KH,Beshiri ML,Agarwal S,Rodriguez-Nieves JA,Capaldo B,Kelly K,VanderWeele DJ

    更新日期:2020-07-01 00:00:00

  • Long-term tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells.

    abstract::Antibody-drug conjugates (ADC) represent a promising therapeutic modality for the clinical management of cancer. We sought to develop a novel ADC that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells (TIC), which comprise the most aggressive cell population in the tumor. We optimized an anti-5T4 A...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-12-0603

    authors: Sapra P,Damelin M,Dijoseph J,Marquette K,Geles KG,Golas J,Dougher M,Narayanan B,Giannakou A,Khandke K,Dushin R,Ernstoff E,Lucas J,Leal M,Hu G,O'Donnell CJ,Tchistiakova L,Abraham RT,Gerber HP

    更新日期:2013-01-01 00:00:00

  • Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies.

    abstract::Histone deacetylase inhibitors represent a promising new class of anticancer agents. In the current investigation, we examined the activity of PXD101, a potent histone deacetylase inhibitor, used alone or in combination with clinically relevant chemotherapeutics (docetaxel, paclitaxel, and carboplatin), in preclinical...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0111

    authors: Qian X,LaRochelle WJ,Ara G,Wu F,Petersen KD,Thougaard A,Sehested M,Lichenstein HS,Jeffers M

    更新日期:2006-08-01 00:00:00

  • The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines.

    abstract::The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Hamdouchi C,Keyser H,Collins E,Jaramillo C,De Diego JE,Spencer CD,Dempsey JA,Anderson BD,Leggett T,Stamm NB,Schultz RM,Watkins SA,Cocke K,Lemke S,Burke TF,Beckmann RP,Dixon JT,Gurganus TM,Rankl NB,Houck KA,Zhang F

    更新日期:2004-01-01 00:00:00

  • Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly.

    abstract::The CDC25 cell cycle regulators are promising targets for new pharmacologic approaches in cancer therapy. Inhibitory compounds such as BN82685 have proven to be effective in specifically targeting CDC25 in cultured cells and in inhibiting tumor cell growth. Here, we report that BN82685 impairs microtubule dynamic inst...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0299

    authors: Cazales M,Boutros R,Brezak MC,Chaumeron S,Prevost G,Ducommun B

    更新日期:2007-01-01 00:00:00

  • Therapeutic potential of antisense oligodeoxynucleotides to down-regulate thymidylate synthase in mesothelioma.

    abstract::Malignant mesothelioma is an aggressive tumor of the serosal surfaces of the lungs, heart, and abdomen. Survival rates are poor and effective treatments are not available. However, recent therapeutic regimens targeting thymidylate synthase (TS) in malignant mesothelioma patients have shown promise. We have reported th...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0073

    authors: Flynn J,Berg RW,Wong T,van Aken M,Vincent MD,Fukushima M,Koropatnick J

    更新日期:2006-06-01 00:00:00

  • First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits β-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer.

    abstract::RX-5902 is a first-in-class anticancer agent targeting phosphorylated-p68 and attenuating nuclear shuttling of β-catenin. The purpose of this study was to evaluate the efficacy of RX-5902 in preclinical models of triple-negative breast cancer (TNBC) and to explore effects on β-catenin expression. A panel of 18 TNBC ce...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-18-1334

    authors: Capasso A,Bagby SM,Dailey KL,Currimjee N,Yacob BW,Ionkina A,Frank JG,Kim DJ,George C,Lee YB,Benaim E,Gittleman B,Hartman SJ,Tan AC,Kim J,Pitts TM,Eckhardt SG,Tentler JJ,Diamond JR

    更新日期:2019-11-01 00:00:00

  • Interactions between PTEN and the c-Met pathway in glioblastoma and implications for therapy.

    abstract::The tyrosine kinase receptor c-Met and its ligand hepatocyte growth factor (HGF) are frequently overexpressed and the tumor suppressor PTEN is often mutated in glioblastoma. Because PTEN can interact with c-Met-dependent signaling, we studied the effects of PTEN on c-Met-induced malignancy and associated molecular eve...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0627

    authors: Li Y,Guessous F,DiPierro C,Zhang Y,Mudrick T,Fuller L,Johnson E,Marcinkiewicz L,Engelhardt M,Kefas B,Schiff D,Kim J,Abounader R

    更新日期:2009-02-01 00:00:00

  • Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs.

    abstract::Floxuridine is a clinically proven anticancer agent in the treatment of metastatic colon carcinomas and hepatic metastases. However, prodrug strategies may be necessary to improve its physiochemical properties and selectivity and to reduce undesirable toxicity effects. Previous studies with amino acid ester prodrugs o...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-04-0290

    authors: Landowski CP,Vig BS,Song X,Amidon GL

    更新日期:2005-04-01 00:00:00

  • Cytochrome P450 1B1 gene polymorphisms as predictors of anticancer drug activity: studies with in vitro models.

    abstract::Cytochrome P450 1B1 (CYP1B1) is found in tumor tissue and is suspected to play a role in oncogenesis and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of developing lung and other cancers. They may be associated with tumor response to anticancer drugs. We have determined 4 frequent nons...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-10-0673

    authors: Laroche-Clary A,Le Morvan V,Yamori T,Robert J

    更新日期:2010-12-01 00:00:00

  • A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers.

    abstract::Conditionally replicating adenoviruses (CRAd) can replicate specifically in cancer cells and lyse them. The CRAds were widely used in the preclinical and clinical studies of cancer therapy. We hypothesize that more precisely regulated replication of CRAds may further improve the vector safety profile and enhance its a...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-2429

    authors: Wang X,Su C,Cao H,Li K,Chen J,Jiang L,Zhang Q,Wu X,Jia X,Liu Y,Wang W,Liu X,Wu M,Qian Q

    更新日期:2008-06-01 00:00:00

  • Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone.

    abstract::Constitutive activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) occurs at very high frequency in various hematopoietic malignancies and solid tumors. It has been demonstrated that the tyrosine kinase inhibitor, AG-490, selectively blocks JAK activity and completely elimina...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Burdelya L,Catlett-Falcone R,Levitzki A,Cheng F,Mora LB,Sotomayor E,Coppola D,Sun J,Sebti S,Dalton WS,Jove R,Yu H

    更新日期:2002-09-01 00:00:00

  • Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress: a role of Bcl-2.

    abstract::Arsenic trioxide (As(2)O(3)) has been used successfully in the treatment of acute promyelocytic leukemia. However, effects of As(2)O(3) in normal peripheral blood T cells have not been studied in detail. The purpose of this study was to investigate whether As(2)O(3) would induce apoptosis in normal T cells and therefo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Gupta S,Yel L,Kim D,Kim C,Chiplunkar S,Gollapudi S

    更新日期:2003-08-01 00:00:00

  • Camptothecin poly[n-(2-hydroxypropyl) methacrylamide] copolymers in antitopoisomerase-I tumor therapy: intratumor release and antitumor efficacy.

    abstract::Soluble copolymers of camptothecin (CPT), based on poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA), were obtained by conjugation through the degradable spacers -Gly-Phe-Leu-Gly- or -Gly-6-aminohexanoyl-Gly-. We investigated to what extent passive accumulation and retention of hydroxypropyl methacrylamide copolymer of...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Zamai M,VandeVen M,Farao M,Gratton E,Ghiglieri A,Castelli MG,Fontana E,D'Argy R,Fiorino A,Pesenti E,Suarato A,Caiolfa VR

    更新日期:2003-01-01 00:00:00

  • Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage.

    abstract::AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinom...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-2362

    authors: Yan Y,Su X,Liang Y,Zhang J,Shi C,Lu Y,Gu L,Fu L

    更新日期:2008-06-01 00:00:00

  • KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling.

    abstract::Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0183

    authors: Feng R,Ma H,Hassig CA,Payne JE,Smith ND,Mapara MY,Hager JH,Lentzsch S

    更新日期:2008-06-01 00:00:00

  • Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

    abstract::Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0337

    authors: Talbert EE,Yang J,Mace TA,Farren MR,Farris AB,Young GS,Elnaggar O,Che Z,Timmers CD,Rajasekera P,Maskarinec JM,Bloomston M,Bekaii-Saab T,Guttridge DC,Lesinski GB

    更新日期:2017-02-01 00:00:00

  • Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer.

    abstract::Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of dissemi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-14-0658

    authors: Sato K,Hanaoka H,Watanabe R,Nakajima T,Choyke PL,Kobayashi H

    更新日期:2015-01-01 00:00:00

  • Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase.

    abstract::Eribulin (E7389), a synthetic analogue of halichondrin B in phase III clinical trials for breast cancer, binds to tubulin and microtubules. At low concentrations, it suppresses the growth phase of microtubule dynamic instability in interphase cells, arrests mitosis, and induces apoptosis, suggesting that suppression o...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0095

    authors: Okouneva T,Azarenko O,Wilson L,Littlefield BA,Jordan MA

    更新日期:2008-07-01 00:00:00

  • A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types.

    abstract::Urokinase plasminogen activator (uPA) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. Due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. These have m...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0315

    authors: Abi-Habib RJ,Singh R,Liu S,Bugge TH,Leppla SH,Frankel AE

    更新日期:2006-10-01 00:00:00