57th ASH Annual Meeting and Exposition (December 5-8, 2015): 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster I

Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents Oral and Poster Abstracts
Poster

Hall A, Level 2 (Orange County Convention Center)

IMGN529, a Novel Antibody-Drug Conjugate (ADC) Targeting CD37 Shows Synergistic Activity with Rituximab in Non-Hodgkin Lymphoma (NHL) Models

Jutta Deckert, PhD¹, Callum M Sloss, PhD²^*, Katie O'Callaghan, PhD³^*, Jenny Tsui, BS³^*, Nemisha Dawra, BS²^*, Yong Yi, MD¹^*, Jennifer A Coccia, BS³^*, Leanne Lanieri, BS³^*, Sharon Chicklas, BS¹^* and Angela Romanelli, PhD⁴

¹Discovery Research, ImmunoGen, Inc., Waltham, MA
²Biomarkers, ImmunoGen, Inc., Waltham, MA
³Pharmacology Toxicology, ImmunoGen, Inc., Waltham, MA
⁴ImmunoGen, Inc., Waltham, MA

1549

Activity of PIM Kinases in Chronic Lymphocytic Leukemia Modulates Tumor Cell Survival and Stromal Interactions through a Pleiotropic Mechanism Involving Modulation of CXCR4 - mTOR Pathway

Emilia Bialopiotrowicz, PhD¹^*, Patryk Gorniak, PhD¹^*, Maciej Szydlowski, PhD¹^*, Tomasz Sewastianik, MSc¹^*, Przemyslaw Kiliszek, MSc¹^*, Anna Polak, MSc¹^*, Ewa Jablonska, PhD¹^*, Bozena Katarzyna Budziszewska, MD, PhD^2,3^*, Bartosz Pula, MD³^*, Maja Wasylecka, MD³^*, Katarzyna Borg, PhD¹^*, Hanna Makuch-Lasica, MSc¹^*, Grazyna Nowak, MSc¹^*, Ewa Lech-Maranda, MD, PhD^2,3^*, Krzysztof Warzocha, MD, PhD³^*, Wojciech Czardybon, PhD⁴^*, Michal Galezowski, PhD⁴^*, Renata Windak, PhD⁴^*, Krzysztof Brzozka, PhD⁴^* and Przemyslaw Juszczynski, MD, PhD¹^*

¹Dept. of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
²Centre of Postgraduate Medical Education, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
³Dept. of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
⁴Selvita S.A., Cracow, Poland

1550

Comparative Phosphoproteomics Study Between Obinutuzumab (GA101) Vs. Rituximab (RTX) Against RTX Sensitive/Resistant Burkitt Lymphoma (BL): Differentially Phosphorylated B Cell Receptor, Fc-Gamma Receptor, Phagocytosis and Natural Killer Cell-Mediated Cytotoxicity Signaling Pathway Proteins

Aradhana Tiwari¹^*, Delphine CM Rolland, PharmD, PhD²^*, Mona Elmacken, MD¹^*, Janet Ayello, MS¹^*, Carmella van de Ven, MA¹^*, Venkatesha Basrur, Phd²^*, Kevin Conlon, MS²^*, Damine Fermin, PhD²^*, Matthew J. Barth, MD³, Christian Klein, PhD⁴, Kojo Elenitoba-Johnson², Megan S Lim, MD, PhD² and Mitchell S. Cairo, MD^1,5,6,7,8

¹Pediatrics, New York Medical College, Valhalla, NY
²Pathology, University of Michigan Medical School, Ann Arbor, MI
³Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY
⁴Roche Innovation Center Zurich, Schlieren, Switzerland
⁵Pathology, New York Medical College, Valhalla, NY
⁶Microbiology & Immunology, New York Medical College, Valhalla, NY
⁷Medicine, New York Medical College, Valhalla, NY
⁸Cell Biology & Anatomy, New York Medical College, Valhalla, NY

1551

Alisertib, an Aurora a Kinase Inhibitor, Induces Synthetic Lethality and Overcomes Chemoresistance in Myc-Overexpressing Lymphoma Cells

Steven I. Park, MD, Carolina P. Lin, MS^*, Dirk P. Dittmer, PhD^*, Steven P. Angus, PhD^*, Greg G. Wang, PhD^*, Yuri D. Fedoriw, MD, David B. Darr, BS^*, Daniel P. Roth, BS^*, Norman E. Sharpless, MD and Blossom Damania, PhD^*

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC

1552

Systemic Antitumor Effects of Intratumoral Administration of the Novel Immunotherapeutic Combination Anti-CTLA4, Anti-CD137, and Anti-OX40 in Mouse Models of Lymphoma and Solid Tumor

Hebb Jonathan, MD, MSc¹^* and Holbrook E Kohrt, MD, Ph.D.²

¹Stanford University, Stanford, CA
²Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA

1553

Targeting Lymphoma By the Bi-Functional Hexameric Fusion Protein CTLA4-Fasl; Mode-of-Action, Pre-Clinical Efficacy and Toxicology Studies

Alexandra Aronin¹^*, Shira Amsili²^*, Tatyana Prigozhina¹^*, Moshe Baru²^*, Efi Makdasi²^*, Kobi Tzdaka²^*, Fanny Shkedy²^*, Noam Shani²^* and Michal Dranitzki Elhalel¹^*

¹Nephrology and Hypertension, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
²KAHR Medical LTD, Jerusalem, Israel

1554

eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL)

Kevin R. Webster, Ph.D.¹^*, Vikas K Goel, Ph.D.¹^*, Ivy NJ Hung, Ph.D.¹^*, Gregory S Parker, Ph.D.¹^*, Jocelyn Staunton, BA¹^*, Melissa Neal¹^*, Jolene Molter¹^*, Gary G Chiang, Ph.D.¹^*, Katti A. Jessen, PhD², Christopher J Wegerski, Ph.D.¹^*, Samuel Sperry, Ph.D.¹^*, Vera Huang, Ph.D.¹^*, Joan Chen, Ph.D.¹^*, Peggy A Thompson, Ph.D.¹^*, James R Appleman, Ph.D.¹^*, Stephen E Webber, Ph.D.¹^*, Paul A Sprengeler, Ph.D.¹^* and Siegfried H Reich, Ph.D.¹^*

¹Effector Therapeutics, San Diego, CA
²Pfizer, San Diego, CA

1555

The PI3 Kinase (PI3K) Inhibitor, Buparlisib/BKM120, in B-Cell, T-Cell and Hodgkin Lymphoma Cell Lines: Cell Death Studies and Examination of Genomic Pathway Analyses Via a Systems Biology Approach

Michael E Coyle, MD¹, Ravi Dashnamoorthy, PhD², Afshin Beheshti, PhD²^* and Andrew M. Evens, DO, MSc³

¹Division of Hematology/Oncology, Tufts Medical Center, Boston, MA
²Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA
³Tufts Medical Center Cancer Center, Boston, MA

1556

Novel Alkylating Agent, Ureidomustine Exhibit Pre-Clinical Efficacy in B-Cell Lymphoma with Minimal Dose-Limiting Myelotoxicity

Eloisi Caldas Lopes^1,2^*, Shieh Jae-Hung¹^*, Srikanth Ambati¹^*, Su Tsann-Long³^*, Fabian Correa¹^*, Elizabeth Peguero¹^* and Malcolm A.S. Moore¹

¹Cell Biology, Memorial Sloan Kettering Cancer Center, New York
²BOtique Biopharm, Taipei, Taiwan
³Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan

1557

Identification of USP14 and UCHL5 As Druggable Oncotargets in Ibrutinib-Resistant Mantle Cell Lymphoma

Aneel Paulus, MD, MS¹, Sharoon Akhtar, MPhil²^*, Kelara Samuel³^*, Hassan Yousaf⁴^*, Davitte Cogen⁴^*, Pooja Advani, MBBS⁵^*, Thomas E. Witzig, MD⁶, George J Weiner, MD⁷, Sikander Ailawadhi, MD⁸, Joachim Gullbo, MD, PhD⁹^*, Stig Linder, Ph.D¹⁰^*, Geraldo Otero-Colon³^*, Kasyapa S. Chitta, PhD¹ and Asher Alban Chanan-Khan, MD⁸

¹Cancer Biology, Mayo Clinic, Jacksonville, FL
²Department of Cancer Biology, Mayo Clinic, Jacksonville, FL
³Mayo Clinic, Jacksonville
⁴Mayo Clinic, Jacksonville, FL
⁵Division of Hematology & Medical Oncology, Mayo Clinic, Jacksonville, FL
⁶Division of Hematology, Mayo Clinic, Rochester, MN
⁷University of Iowa, Iowa City, IA
⁸Division of Hematology & Oncology, Mayo Clinic, Jacksonville, FL
⁹Uppsala University, Uppsala, Sweden
¹⁰Karolinska, Stockholm, Sweden

1558

PI3K/Akt/mTOR Pathway Inhibition in Chemotherapy-Sensitive and -Resistant Models of Burkitt Lymphoma

Maria Bhatti, MD¹^*, Thomas Ippolito, MS²^*, Cory Mavis, BSc, MSc³^* and Matthew J. Barth, MD^1,2

¹Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY
²Department of Pediatrics, University at Buffalo, Buffalo, NY
³Departments of Immunology and Medicine, Roswell Park Cancer Institute, Buffalo, NY

1559

Mechanistic and Pharmacodynamic Studies of Adct-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Michael J. Flynn, MD^1,2^*, Patrick H. van Berkel, PhD³^*, Francesca Zammarchi, PhD³^*, Peter C. Tyrer, PhD²^*, Ayse U. Akarca¹^*, Narinder Janghra¹^*, Vishvesh Shende, PhD¹^*, Joseph Linares¹^*, Teresa Marafioti, MD¹^*, David G. Williams, PhD²^*, Philip W. Howard, PhD^2,3^* and John A. Hartley, PhD^1,2,3^*

¹University College London, London, United Kingdom
²Spirogen/Medimmune, London, United Kingdom
³ADC Therapeutics, Epalinges, Switzerland

1560

Aurora Plus PI3K Inhibition Abrogates PD-L1 Induction in Peripheral T-Cell Non-Hodgkin Lymphoma

Daruka Mahadevan, MD, PhD¹, Eric Vick, PhD¹, Bryan Huber, M.D.¹^*, Carla Morales, B.S.¹^*, Laurence Cooke, M.S.¹^*, Catherine M. Spier, MD² and Wenqing Qi, Ph.D.¹^*

¹University of Tennessee Health Science Center, West Cancer Center, Memphis, TN
²University of Arizona, Tucson, AZ

1561

Synergistic Induction of Cell Death in Hodgkin Lymphoma Cells By the Novel PI3K Inhibitor RP6530 Combined with Brentuximab Vedotin (SGN-35) through Inhibition of Tumor Angiogenesis

Silvia Laura Locatelli, PhD¹^*, Giuseppa Careddu¹^*, Armando Chierchia¹^*, Srikant Viswanadha, PhD²^*, Swaroop Vakkalanka, PhD³^*, Luca Castagna⁴^*, Armando Santoro, MD^4,5^* and Carmelo Carlo-Stella, MD^4,6

¹Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Italy
²Incozen Therapeutics Pvt. Ltd., Hyderabad, India
³Rhizen Pharmaceuticals SA, La Chaux-de-Fonds, Switzerland
⁴Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Italy
⁵Humanitas University, Rozzano, Italy
⁶Department of Medical Biotechnology and Translational Medicine, University of Milano, Milano, Italy

1562

The Combination of Belinostat with Zidovudine for Treatment of HTLV-I Related Adult T-Cell Leukemia-Lymphoma

Ngoc Toomey¹^* and Juan Carlos Ramos, MD²

¹Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
²Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL

1563

Targeting Myddosome Self-Assembly in Waldenstrom's Macroglobulinemia

Xia Liu, MD¹^*, Zachary Hunter, PhD¹^*, Lian Xu¹^*, Jie Chen, PhD¹^*, Jiaji Chen¹^*, Nicholas Tsakmaklis¹^*, Christopher J Patterson, MFA¹^*, Jorge J Castillo, MD¹, Sara Buhrlage, PhD²^*, Nathanael Gray, PhD²^*, Steven P Treon, MD, PhD¹ and Guang Yang, PhD¹

¹Bing Center for WM, Dana Farber Cancer Institute, Boston, MA
²Dept of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA

1564

Pre-Clinical Development of Adct-402, a Novel Pyrrolobenzodiazepine (PBD)-Based Antibody Drug Conjugate (ADC) Targeting CD19-Expressing B-Cell Malignancies

Francesca Zammarchi, PhD¹^*, David G. Williams, PhD²^*, Lauren Adams³^*, Karin Havenith, PhD¹^*, Simon Chivers, PhD¹^*, Francois D'Hooge, PhD³^*, Philip W. Howard, PhD^1,2^*, John A. Hartley, PhD^1,2,4^* and Patrick H. van Berkel, PhD¹^*

¹ADC Therapeutics, Epalinges, Switzerland
²Spirogen/Medimmune, London, United Kingdom
³Spirogen, London, United Kingdom
⁴University College London, London, United Kingdom

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^*signifies non-member of ASH

625.P1.55 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster I