50th ASH Annual Meeting and Exposition (December 6 - 9, 2008): Lymphoma: Pre-Clinical - Chemotherapy and Biologic Agents Poster I

Saturday, December 6, 2008: 5:30 PM-7:30 PM

Hall A (Moscone Center)

Complement (C) Activation Followed by Penetration of the Membrane Attack Complex (MAC) on B Cells Opsonized with CD20 Mabs Allows for Calcium Influx Which Induces Streamers. Generalization of Streaming to Include other Mabs and Target Cells

Ronald P. Taylor, PhD¹, Paul V. Beum, PhD¹^*, P. Todd Stukenberg, PhD¹^*, Andrew W. Pawluczkowycz, MS¹^*, Margaret A. Lindorfer, PhD¹^*, Frank J. Beurskens, PhD²^*, Paul W. H. I. Parren, PhD²^* and Jan G. J. van de Winkel, PhD³^*

¹Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA
²Genmab B. V., Utrecht, Netherlands
³Genmab B. V. and Department of Immunology, UMCU, Utrecht, Netherlands

1578

Binding of Submaximal C1q to B Cells Opsonized with Anti-CD20 Mabs Ofatumumab (OFA) or Rituximab (RTX) Promotes Complement Dependent Cytotoxicity (CDC), and Considerably Higher Levels of CDC Are Induced by OFA Than by RTX

Ronald P. Taylor, PhD¹, Andrew W. Pawluczkowycz, MS¹^*, Margaret A. Lindorfer, PhD¹^*, Jan G. J. van de Winkel, PhD²^*, Frank J. Beurskens, PhD³^* and Paul W. H. I. Parren, PhD³^*

¹Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA
²Genmab B. V. and Department of Immunology, UMCU, Utrecht, Netherlands
³Genmab B. V., Utrecht, Netherlands

1579

A Novel mTOR Kinase Inhibitor Causes Growth Inhibition, Cell Cycle Arrest, Apoptosis and Autophagic Cell Death in Mantle Cell Lymphoma Cell Lines: A Distinct Profile from Rapamycin

Weiming Xu¹^*, Christine Kang¹^*, Mercedes Delgado²^*, Sophie M Perrin-Ninkovic²^*, Patrick W Papa²^*, Jennifer R Riggs²^*, John Sapienza²^*, Ronald J Albers²^*, Branden G.S Lee²^*, Roy L Harris²^*, Deborah S Mortensen²^*, Peter Worland¹^* and Sabita Sankar¹^*

¹Oncology Research, Celgene, San Diego, CA
²Chemistry, Celgene, San Diego, CA

1580

Characterization of MDX-1401, a Human Anti-CD30 Antibody with Enhanced Effector Function, for Therapy of Malignant Lymphoma

Pina M. Cardarelli, PhD.¹^*, Cristina Loomis, PhD.¹^*, Ben Preston¹^*, Amelia Black, PhD.²^*, David Passmore, PhD.³^*, Tseng-Hui Chen, PhD.⁴^*, Sharline Chen¹^*, Jie Liu, PhD.⁴^*, Michelle R Kuhne, PhD¹^*, Mohan Srinivasan, PhD.³^*, Albert Assad, MD⁵, Alison Witte¹^*, Marco Coccia, PhD⁶, Robert F. Graziano, PhD.⁷^* and David J. King, PhD.⁴^*

¹Cell Biology and Pharmacology, Medarex Inc., Sunnyvale, CA
²Research Management, Medarex Inc., Milpitas, CA
³Protein Chemistry, Medarex Inc, Sunnyvale, CA
⁴Biochemistry, Medarex Inc., Sunnyvale, CA
⁵Dept. of Clinical Science, Medarex Inc., Bloomsbury, NJ
⁶Medarex, Inc., Discovery Research, Milpitas, CA
⁷Research Management, Medarex Inc., Bloomsbury, NJ

1581

T Cell Modulation Combined with Intratumoral CpG Cures Lymphoma without the Need for Chemotherapy

Roch Houot, MD¹^* and R. Levy²

¹Medicine / Oncology, Stanford University, Stanford, CA
²Oncology, Stanford University, Stanford, CA

1582

IL-10 Present in the B Lymphoma Microenvironment Drives Macrophages to Efficient Tumour Suppressing Cells with High Phagocytic Activity in Presence of Rituximab

Josee Golay, PhD¹^*, Marzia Leidi, Dr¹^*, Elisa Gotti¹^*, Giuseppe Palumbo, Dr²^* and Martino Introna, MD¹

¹Laboratory of Cellular and Gene Therapy "G. Lanzani", Division of Hematology, Ospedali Riuniti, Bergamo, Italy
²Division of Hematology, Ospedale Ferrarotto, Catania, Italy

1583

Preclinical Analysis of the Combined Activity of SGN-40, Anti-CD40 Monoclonal Antibody, with Rituximab in Non-Hodgkin Lymphoma

Timothy S. Lewis¹^*, Renee S. McCormick¹^*, Julie A. McEarchern¹^*, Kim Kissler²^*, Ivan J. Stone²^*, Hans-Peter Gerber²^*, Jonathan G. Drachman³^*, Iqbal Grewal¹ and Che-Leung Law¹^*

¹Molecular Oncology & Immunology, Seattle Genetics, Inc., Bothell, WA
²Translational Biology, Seattle Genetics, Inc.
³Early Clinical Development, Seattle Genetics, Inc.

1584

A Promising Therapeutic Implication of a Novel Bcl-2 Family Inhibitor ABT-737 for Adult T-Cell Leukemia/Lymphoma

Kenji Ishitsuka, M.D., Ph.D.¹, Fusanori Yotsumoto, M.D.²^*, Hiroo Katsuya, M.D.¹^*, Emiko Ushijima¹^*, Shingo Miyamoto, M.D., Ph.D.²^* and Kazuo Tamura, M.D., Ph.D.¹^*

¹Department of Internal Medicine, Division of Hematology and Oncology, Fukuoka University, Fukuoka, Japan
²Department of Biochemistry, School of Medicine, Fukuoka University, Fukuoka, Japan

1585

Compared Antitumor Activity of GA101 and Rituximab against the Human RL Follicular Lymphoma Xenografts in SCID Beige Mice

Stéphane Dalle¹^*, Lina Reslan²^*, Stéphanie Brunet Manquat²^*, Franck Herting³^*, Christian Klein³^*, Pablo Umana⁴^* and Charles Dumontet⁵

¹Hospices Civils de Lyon, Lyon, France
²University of Lyon, Lyon, France
³Roche, Penzberg, Germany
⁴Glycart Biotechnology, Zurich, Switzerland
⁵Laboratoire Hematology, Hopital Edouard Herriot, Lyon, France

1586

Combined Treatment with Short Synthetic Anti-Lymphoma Peptide and CpG ODN; A Therapeutic Vaccine Which cures the A20 Lymphoma in Balb/C Mice

Arne Kolstad, MD, PhD¹^*, Roch Houot, MD²^*, Gerd Berge³^*, Øystein Rekdal, PhD³^*, Debra Czerwinski, PhD²^*, Matthew Goldstein²^*, Joshua Brody, MD² and R. Levy⁴

¹Oncology, The Norwegian Radium Hospital, Oslo, Norway
²Medicine / Oncology, Stanford University, Stanford, CA
³Biochemistry, University of Tromsø, Tromsø, Norway
⁴Oncology, Stanford University, Stanford, CA

1587

The Histone Deacetylase Inhibitor Vorinostat Induces Apoptosis in T-Cell Lymphoma Cell Lines and Synergizes with Bortezomib

Jennifer L. Cultrera, MD¹, Lauren Rosenberg¹^*, David J. McConkey, PhD²^* and Barbara Pro, MD³^*

¹Division of Cancer Medicine, M. D. Anderson Cancer Center, Houston, TX
²Department of Urology, M. D. Anderson Cancer Center, Houston, TX
³Department of Lymphoma and Myeloma, M. D. Anderson Cancer Center, Houston, TX

1588

Radioimmunotherapy of Non-Hodgkin Lymphoma is Improved without Increasing Toxicity by Combination with Antibody immunotherapy

Robert M Sharkey, Ph.D.¹^*, M. Jules Mattes, Ph.D.¹^*, Habibe Karacay, Ph.D.¹^*, Chien-Hsing Chang, PhD²^*, Edmund A Rossi, PhD³^*, William J McBride, Ph.D.⁴^* and David M. Goldenberg, ScD, MD¹

¹Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ
²Molecular Biology, Immunomedics, Inc., Morris Plains, NJ
³Molecular Biology, IBC Pharmaceuticals, Inc., Morris Plains, NJ
⁴Chemistry, Immunomedics, Inc., NJ, NJ

1589

In-Vitro Treatment with the AKT-Inhibitor GSK 690693 Induces Cell Death in Lymphoma Cell Lines and in Primary CLL Cells and Is Followed by Caspase-3 Activation and Cytochrome C Release

Dirk Winkler^*, Thorsten Zenz^*, Daniel Mertens^*, Annett Habermann^*, Hartmut Döhner^* and Stephan Stilgenbauer

University of Ulm, Ulm, Germany

1590

A Novel Anti-CD20 IgG-Interferon-α2b Fusion Protein with Potent in Vitro and in Vivo Anti-Lymphoma Activity Made by the Dock-and-Lock (DNL) Method

Edmund A Rossi, PhD¹^*, Chien-Hsing Chang, PhD¹^*, Thomas M Cardillo, PhD¹^*, Diane L Nordstrom¹^* and David M. Goldenberg, ScD, MD²

¹R&D, Immunomedics, Inc., Morris Plains, NJ
²Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ

1591

Bispecific Anti-CD20/Anti-CD22 Antibodies with Potent Lymphoma Cytotoxicity

Edmund A Rossi, PhD¹^*, Chien-Hsing Chang, PhD¹^*, Thomas M Cardillo, PhD¹^*, Rhona Stein, PhD²^*, Diana Pilas¹^*, Diane L Nordstrom¹^*, John Kopinski¹^* and David M. Goldenberg, ScD, MD²

¹R&D, Immunomedics, Inc., Morris Plains, NJ
²Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ

1592

Anti-Tumor Activity of the Aurora a Inhibitor MLN8237 in Diffuse Large B-Cell Lymphoma Preclinical Models

Jessica J Huck, BA^*, Mengkun Zhang, MD^*, Marc L Hyer, PhD^* and Mark G Manfredi, PhD^*

Oncology, Millennium: The Takeda Oncology Company, Cambridge, MA

1593

Identification of a Diagnostic Gene Signature for SGN-40, Anti-CD40 Monoclonal Antibody, in Pre-Clinical NHL Models and the Role of FAS in SGN-40 Mediated Apoptosis

Xiaoyan Shi, Ph.D¹^*, Bart Burington, Ph.D²^*, Tom Januario¹^*, Jeffrey T Lau³^*, Shang-Fan Yu³^*, Allen Ebens, Ph.D³^* and David Dornan, Ph.D¹^*

¹Research Oncology Diagnostics, Genentech, Inc, South San Francisco, CA
²Early Clinical Development Biostatistics, Genentech, Inc, South San Francisco, CA
³Translational Oncology, Genentech, Inc., South San Francisco, CA

1594

Cytotoxic Activity of Histone Deacetylase Inhibitor ITF2357 on Burkitt's Lymphoma Cell Lines Is Associated to Micro-RNA Modulation and Transglutaminase 2 Restoration

Roberta Zappasodi¹^*, Massimo Di Nicola¹, Francesca Baldan¹^*, Marilena V Iorio²^*, Michele Magni¹^*, Elda Tagliabue²^*, Carlo M. Croce, MD³, Carmelo Carlo-Stella¹^* and Alessandro M. Gianni¹^*

¹"C. Gandini" Bone Marrow Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
²Molecular Biology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
³The Ohio State University Comprehensive Cancer Center, Columbus, OH

1595

Inhibition of Human Lymphoma Cell Growth by the PKC-Beta Selective Inhibitor Enzastaurin (LY317615) in Combination with Multiple Therapeutic Agents

Randall M Rossi^*, Marlene Balys^*, Dean Franklin^*, Valerie Grose^*, Richard I Fisher^* and Craig Jordan

James P Wilmot Cancer Center, University of Rochester, Rochester, NY

1596

Molecular Mechanism by Which Rituximab Sensitizes B-NHL Cells to TRAIL Apoptosis: Induction of RKIP and DR5 Expression Via Inhibition of NF-Kb, Snail, and YY1

Mario I. Vega, PhD¹, Melisa Martinez-Paniagua¹^*, Sara Huerta-Yepez, PhD.²^*, Yeung Kam³^*, Stavroula Baritaki⁴^* and Benjamin Bonavida, PhD⁵

¹Hosp. de Infect., CMN La Raza IMSS, Mexico, DF, Mexico
²Unidad de Investigacion en Enfermedades Oncologcias,, Hospital Infantil de Mexico, Federico Gomez, SSA, Mexico, Mexico City, Mexico
³Biochemistry and Molecular Biology, Medical Collage of Ohio, Toledo, OH
⁴Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA
⁵University of CA, Los Angeles, Los Angeles, CA

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^*signifies non-member of ASH

625.P1.52 Lymphoma: Pre-Clinical - Chemotherapy and Biologic Agents Poster I