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Cancer

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Supplement: Cancer Therapy With Antibodies and Immunoconjugates, Supplement to Cancer

15 February 2010

Volume 116, Issue S4

Pages i–ii, 1011–1145

  1. Supplement

    1. Top of page
    2. Supplement
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      Introduction to the supplement, “Cancer Therapy with Antibodies and Immunoconjugates” (pages 1011–1012)

      David M. Goldenberg

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24786

      This supplement includes 16 representative articles presented at the 12th Conference on Cancer Therapy With Antibodies and Immunconjugates, Parsippany, New Jersey, October 16-18, 2008, encompassing cancer treatment with unconjugated and isotope-conjugated antibodies targeting selective cancer biomarkers.

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      Targeting FMS-related tyrosine kinase receptor 3 with the human immunoglobulin G1 monoclonal antibody IMC-EB10 (pages 1013–1017)

      Hagop Youssoufian, Eric K. Rowinsky, James Tonra and Yiwen Li

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24787

      FMS-related tyrosine kinase receptor 3 (FLT3)-directed agents hold considerable promise in hematologic malignancies. IMC-EB10, a fully human monoclonal antibody targeting FLT3, was active in leukemia preclinical models and was the first antibody to enter clinical development in this setting.

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      Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor α (pages 1018–1026)

      Gaurav D. Shah, Nick Loizos, Hagop Youssoufian, Jonathan D. Schwartz and Eric K. Rowinsky

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24788

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      The platelet-derived growth factor (PDGF)/PDGF receptor α (PDGFRα) signaling axis is a rational target for anticancer therapeutic development, because it plays a critical role in cancer growth, survival, and metastasis and in modulation of the stromal and angiogenic support for cancer growth. This article reviews the rationale for targeting the PDGF/PDGFRα signaling axis and focuses on IMC-3G3, a fully human immunoglobulin G subclass 1 antibody that targets PDGFRα. IMC-3G3 is undergoing early clinical development as an anticancer therapeutic.

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      Vascular endothelial growth factor receptor-1 in human cancer : Concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1) (pages 1027–1032)

      Jonathan D. Schwartz, Eric K. Rowinsky, Hagop Youssoufian, Bronislaw Pytowski and Yan Wu

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24789

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      Vascular endothelial growth factor receptor-1 (VEGFR-1) mediated signaling contributes to cancer pathogenesis by means of both direct growth stimulation and activation of endothelial, stromal, progenitor, and other cells. Antibody-mediated inhibition of VEGFR-1 represents a promising anti-cancer strategy and preliminary clinical studies investigating IMC-18F1 in humans indicate a favorable safety profile.

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      Toxicity-reducing potential of extracorporeal affinity adsorption treatment in combination with the auristatin-conjugated monoclonal antibody BR96 in a syngeneic rat tumor model (pages 1033–1042)

      Rune Nilsson, Linda Mårtensson, Sophie E. Eriksson, Hans-Olov Sjögren and Jan Tennvall

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24790

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      Extracorporeal affinity adsorption treatment can be used to reduce the toxicity associated with administration of monomethylauristatin FBR96 conjugates, making it possible to increase the amount of conjugates administered.

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      High-dose radioimmunotherapy combined with extracorporeal depletion in a syngeneic rat tumor model : Evaluation of toxicity, therapeutic effect, and tumor model (pages 1043–1052)

      Linda Mårtensson, Rune Nilsson, Tomas Ohlsson, Hans-Olov Sjögren, Sven-Erik Strand and Jan Tennvall

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24791

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      Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. Because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity.

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      Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma (pages 1053–1058)

      Pierre-Yves Salaun, Caroline Bodet-Milin, Eric Frampas, Aurore Oudoux, Catherine Saï-Maurel, Alain Faivre-Chauvet, Jacques Barbet, François Paris and Françoise Kraeber-Bodéré

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24792

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      A pretreatment with bevacizumab may improve radioimmunotherapy efficacy and offer acceptable toxicity in medullary thyroid carcinoma.

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      Improved efficacy of α-particle–targeted radiation therapy : Dual targeting of human epidermal growth factor receptor–2 and tumor-associated glycoprotein 72 (pages 1059–1066)

      Diane E. Milenic, Erik D. Brady, Kayhan Garmestani, Paul S. Albert, Alia Abdulla and Martin W. Brechbiel

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24793

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      The authors investigated the potential of targeting 2 distinct molecules in tumors with high linear energy transfer radioimmunotherapy for the management and treatment of cancer patients who presented with disseminated peritoneal disease. The intent of developing a treatment regimen using α-targeted radiation was to expand the therapeutic repertoire to patient populations beyond those with pancreatic or ovarian cancer to patients with cancers of the colon, stomach, and small intestine, which result in peritoneal carcinomatosis, and to patients with peritoneal mesothelioma.

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      The influence of proteasome inhibitor MG132, external radiation, and unlabeled antibody on the tumor uptake and biodistribution of 188Re-labeled anti-E6 C1P5 antibody in cervical cancer in mice (pages 1067–1074)

      Rébécca Phaeton, Xing Guo Wang, Mark H. Einstein, Gary L. Goldberg, Arturo Casadevall and Ekaterina Dadachova

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24794

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      The efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of human papillomavirus (HPV) type 16 (HPV‒16)-related and HPV18-related cervical cancer would depend on the level and accessibility of intranuclear E6 protein in the tumor. The authors demonstrated that pretreatment of CasKi HPV16-positive tumors in mice with proteasome inhibitor MG132 significantly increased the uptake of radiolabeled anti-E6 antibody in the tumor and cleared quickly from all normal tissues.

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      Anti–prostate-Specific membrane antigen-based radioimmunotherapy for prostate cancer (pages 1075–1083)

      Scott T. Tagawa, Himisha Beltran, Shankar Vallabhajosula, Stanley J. Goldsmith, Joseph Osborne, Dan Matulich, Kristen Petrillo, Sarojben Parmar, David M. Nanus and Neil H. Bander

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24795

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      J591 is a deimmunized monoclonal antibody against prostate-specific membrane antigen. Radiolabeled J591 has been demonstrated to have excellent targeting of prostate cancer metastases, is well tolerated, and has clinical efficacy.

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      177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy (pages 1084–1092)

      Michael Garkavij, Mattias Nickel, Katarina Sjögreen-Gleisner, Michael Ljungberg, Tomas Ohlsson, Karin Wingårdh, Sven-Erik Strand and Jan Tennvall

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24796

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      Three different methods were used to evaluate the absorbed dose to the kidneys in patients with disseminated neuroendocrine tumors treated with 177Lu-(DOTA0,Tyr3) octreotate. Dosimetry based on planar images generally gave higher absorbed dose values compared with methods including single-photon emission computed tomography (SPECT) data. Two different SPECT-based methods gave similar values, although the calculations were based on different assumptions.

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      Three methods assessing red marrow dosimetry in lymphoma patients treated with radioimmunotherapy (pages 1093–1100)

      Ludovic Ferrer, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, Caroline Rousseau, Stephen Le Gouill, William A. Wegener, David M. Goldenberg and Manuel Bardiès

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24797

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      This study shows that image-based red marrow absorbed dose determination is useful to predict hematological toxicity in NHL patients treated with 90Y-labeled epratuzumab.

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      In vitro evaluation of avidin antibody pretargeting using 211At-labeled and biotinylated poly-L-lysine as effector molecule (pages 1101–1110)

      Sofia HL Frost, Holger Jensen and Sture Lindegren

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24798

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      A full scale avidin-biotin pretargeting system was evaluated in vitro, showing high binding of pretargeting molecule to tumor cells, as well as high binding of effector molecule to pretargeted tumor cells.

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      Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab′)2 antibody (pages 1111–1117)

      Frits Aarts, Otto C. Boerman, Robert M. Sharkey, Thijs Hendriks, Chien-Hsing Chang, William J. McBride, Robert P. Bleichrodt, Wim J. G. Oyen and David M. Goldenberg

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24799

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      In an open-label, single-arm trial that assessed a pretargeting procedure for diagnostic imaging of carcinoembryonic antigen-expressing colorectal cancer, the best imaging results were produced 24 hours after 111In-labeled peptide administration using a 4-day interval between injection of the bispecific antibody and the peptide.

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      Pretargeted radioimmunotherapy in rapidly progressing, metastatic, medullary thyroid cancer (pages 1118–1125)

      Françoise Kraeber-Bodéré, Pierre-Yves Salaun, Aurore Oudoux, David M. Goldenberg, Jean-François Chatal and Jacques Barbet

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24800

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      Currently there is no approved drug for the systemic treatment of patients with rapidly progressing metastatic medullary thyroid carcinoma. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit in such patients.

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      Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas (pages 1126–1133)

      M. Corinna A. Palanca-Wessels and Oliver W. Press

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24801

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      Radioimmunotherapy (RIT) has emerged as a valid treatment strategy for lymphoma patients based on the favorable results of a growing number of clinical trials. Various approaches designed to further improve effectiveness and reduce toxicity of RIT are summarized in this review.

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      Improving the treatment of non-Hodgkin lymphoma with antibody-targeted radionuclides (pages 1134–1145)

      Robert M. Sharkey, Habibe Karacay and David M. Goldenberg

      Version of Record online: 2 FEB 2010 | DOI: 10.1002/cncr.24802

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      Radioimmunotherapy is a safe and effective treatment of non-Hodgkin lymphoma that combines an anti-CD20 IgG radioconjugate with a large amount of unlabeled anti-CD20 antibody intended to allow the radioimmunoconjugate to bypass the CD20 antigen sink, but in excess, it could compromise the efficacy of the radioconjugate. Other approaches, such as combining anti-CD20 antibody therapy with radioimmunoconjugate that binds to another B-cell specific antigen, can enhance responses, or in the case of pretargeting procedures with consolidation anti-CD20 antibody therapy, enhance responses with reduced toxicity.

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