DOCSLIB.ORG

Phase I Clinical Trial of the Chimeric Monoclonal Antibody (C30.6) in Patients with Metastatic Colorectal Cancer1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phase I Clinical Trial of the Chimeric Monoclonal Antibody (C30.6) in Patients with Metastatic Colorectal Cancer1 4674 Vol. 6, 4674–4683, December 2000 Clinical Cancer Research Phase I Clinical Trial of the Chimeric Monoclonal Antibody (c30.6) in Patients with Metastatic Colorectal Cancer1 Robyn L. Ward,2 Deborah Packham, uptake. At the 50 mg/m2 level the half-life and maximum -Anne M. Smythe, Jayne Murray, serum concentration were 81 ؎ 15 h and 7.9 ␮g/ml, respec Peter Anderson-Stewart, Neil Kitchen, tively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomog- Rosyln Muirhead, Peter Phillips, Peter Gray, raphy, positron emission tomography scanning, and serial Grant Bigg-Wither, Krishnan Prabakaran, carcinoembryonic antigen measurements. There were no Judy Freund, Michael Fullham, Michele Rule, partial responses, although positron emission tomography David Dalley, Alan Meagher, scanning demonstrated some reduction in tumor activity in Nicholas J. Hawkins, and Glenn M. Smith three individuals. The chimerized c30.6 antibody is not immunogenic in Cooperative Research Centre for Biopharmaceutical Research Ltd., Darlinghurst 2010, New South Wales [R. L. W., D. P., A. M. S., P. A- humans and appears worthy of further study. It does, how- S., N. K., R. M., P. P., G. M. S.]; Departments of Medical Oncology ever, produce a unique profile of side effects that can be well [R. L. W., M. R., D. D.], Nuclear Medicine [K. P., J. S.], Colorectal controlled with premedication. Surgery [A. M.], and Radiology [G. B-W.], St. Vincent’s Hospital, Darlinghurst 2010, New South Wales; Schools of Biotechnology [N. K., P. P., P. G., G. M. S.] and Pathology [R. L. W., N. J. H.], INTRODUCTION University of New South Wales, Sydney 2052, New South Wales; Over the last few years, a number of clinical studies have and Department of Nuclear Medicine [M. F.], Royal Prince Alfred provided evidence that monoclonal antibodies are of value in the Hospital, Sydney 2050, New South Wales, Australia treatment of a variety of cancers, including breast, lymphoma and colorectal tumors (1–3).3,4 Although adjuvant chemother- ABSTRACT apy modestly improves the disease-free and overall survival of patients with Dukes stage C colorectal cancer, there is a need for The murine antibody 30.6 recognizes an antigen that is new adjuvant therapies that have both improved efficacy and expressed on a high proportion of colorectal carcinomas and fewer side effects. In this regard, the proven efficacy of adjuvant their metastases. We report the results of single-dose esca- 17-1A therapy in a small group of patients with Dukes stage C lation studies of the chimeric 30.6 (c30.6) monoclonal anti- colon cancer has shown that antibodies may have optimal effi- body in metastatic colorectal cancer, to evaluate its safety, cacy when used in the setting of minimal residual disease (2). pharmacokinetics, and biodistribution. Furthermore, there is a good rationale for the use of combina- Recombinant c30.6 (IgG1␬) antibody was secreted tions of antibodies or indeed for their use with traditional from Chinese hamster ovary cells and purified by a multi- chemotherapy, so as to deliver a range of potentially synergistic step chromatography process. Seventeen patients with met- antitumor activities (4–6). astatic colorectal cancer were enrolled in this dose escalation The murine monoclonal antibody 30.6 recognizes an anti- study. The first four patients were treated with 3 mg of 123 gen that is expressed on colorectal carcinomas and their metas- I-labeled c30.6, whereas the next 13 received a single dose 2 tases. Expression of the antigen is greatest on well-differentiated of unlabeled antibody (maximum dose, 50 mg/m ). colorectal adenocarcinomas, is less pronounced on poorly dif- The most frequent side effect was a novel syndrome of ferentiated adenocarcinomas, and is usually absent from most severe burning and erythema of the face, chest, neck, ears, undifferentiated carcinomas (7). The biochemical nature of the palms, soles, and genitalia. The frequency of this syndrome 30.6 antigen has not been elucidated, but it is expressed only on was markedly reduced in those patients premedicated with the luminal surface of glandular cells and is not released into the high doses of histamine receptor 1 and histamine receptor 2 circulation. The antigen is found in gastrointestinal epithelium blockers. Other side effects were mild and predictable. Bio- as well as in pancreatic acini, hepatocytes, alveolar pneumo- distribution studies showed a rapid and intensive hepatic cytes, and prostatic acinar epithelium. However, it is not ex- pressed in other organs or tissues of the urogenital tract or central nervous system (7). The murine 30.6 antibody has been shown to localize to s.c. human colorectal cancer xenografts in Received 6/6/00; revised 9/15/00; accepted 9/18/00. The costs of publication of this article were defrayed in part by the nude mice (8) as well as to primary and secondary tumor payment of page charges. This article must therefore be hereby marked deposits in patients with metastatic colorectal cancer (8, 9). advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by the Australian Government Cooperative Research Pro- gram. 2 To whom requests for reprints should be addressed, at Department of 3 Internet address for Rituxan full prescribing information, 2000: http:// Medical Oncology, St. Vincent’s Hospital, Victoria Street; Darlinghurst www.genentech.com/Medicines/rituxan_insert.html. 2010, New South Wales, Australia. Phone: 61292958412; Fax: 4 Internet address for healthcare professionals prescribing information 61283823386; E-mail: [email protected]. for Herceptin, 2000: http://www.herceptin.com/prof/pi000.html. Downloaded from clincancerres.aacrjournals.org on September 27, 2021. © 2000 American Association for Cancer Research. Clinical Cancer Research 4675 Furthermore, the antibody, whether used alone, radiolabeled, or chromatography and then treated with solvent/detergent to in- conjugated to cytotoxic drugs, is able to strongly inhibit the activate lipid-enveloped viruses. Additional purification by an- growth of human colorectal carcinoma xenografts in nude mice ion and cation exchange chromatography removed residual pro- (10). Phase I clinical studies of N-acetylmelphalan coupled to teins, solvent/detergents, and nucleic acids. The purified c30.6 30.6 showed that patients produced a HAMA5 that precluded was additionally purified and formulated into 0.9% saline using additional dosage escalation (11, 12). two gel filtration columns. Finally, the formulated bulk was The development of HAMA could impair the therapeutic sterile- and viral-filtered before dispensing into Hypak glass effectiveness of 30.6, either by interfering with its binding to syringes (Becton Dickinson, Lincoln Park, NJ). Stability studies antigen or by reducing its bioavailability. Replacing the murine showed that the c30.6 antibody was stable in this formulation for constant regions with a human ␥1 region was likely to reduce at least 16 months. Purity, identity, activity, and safety were the immunogenicity of the antibody and also maximize its confirmed before release of the vialed product for clinical use. effector function. Mount et al. described a chimeric version of Radiolabeling of c30.6. The c30.6 antibody (5 mg in 2 ϭ 123 this antibody (c30.6) that binds with moderate affinity (Ka ml) was labeled with I (2 GBq in 1 ml; ARI, Sydney) using 8 Ϫ1 1 ϫ 10 M ) to its antigen and can mediate in vitro ADCC (13). the Iodogen method, and the labeled antibody was purified by Although this chimeric antibody was not able to lyse cells in the gel filtration using a Superose 12 HR column (Pharmacia, presence of either human or rabbit complement, it had antitumor Uppsala, Sweden) coupled with fast protein liquid chromatog- activity in mice with SCID bearing s.c. human colorectal cancer raphy. Before purification, the iodine incorporation was 68.0 Ϯ xenografts. A 40% reduction in tumor size was observed after 7.0%. The immunoreactive fraction of the labeled antibody was i.p. c30.6 administration, with maximal antitumor activity while estimated by the Lindmo method (14) using the human colorec- the c30.6 antibody was being administered. tal cell line HT-29. The average immunoreactivity of the radio- The chimerized 30.6 antibody, therefore, has a number of labeled preparations was 60.7 Ϯ 8.6%. The radiolabeling characteristics that make it an attractive antibody for additional method was validated to produce sterile and pyrogen-free prod- clinical development. These include its ability to induce ADCC, uct. Serum samples from patients injected with radiolabeled its pattern of tissue reactivity, affinity, potential for reduced antibody were analyzed by gel filtration chromatography for the immunogenicity, and documented antitumor activity in animal presence of aggregates and free iodide using a Superose 12 models. We report here the results of single-dose escalation HR10/30 gel filtration column. studies of the chimeric 30.6 monoclonal antibody in patients Patient Selection. For entry to the study, the patients with metastatic colorectal cancer. The primary objectives of the were required to have histologically proven metastatic colorec- study were to evaluate safety, pharmacokinetics, and biodistri- tal cancer and to have adequate renal (creatinine Ͻ125% of the bution of the c30.6 antibody in this patient population. upper limit of the normal range), hepatic (bilirubin Ͻ125% of the upper limit of the normal range; prothrombin time Ͻ 1.3 PATIENTS AND METHODS times control), and hematological function (white blood count Ͼ ϫ 9 Ͼ ϫ 9 Production of c30.6. Recombinant c30.6 (IgG1␬) anti- 4.0 10 /liter; platelet count 100 10 /liter; hemoglobin Ͼ body is secreted from CHO cells. The cloned 30.6 antibody 100 g/liter) as well as the presence of measurable metastatic Ն heavy- and light-chain, variable region cDNAs (obtained from disease (at least one site 1 cm). Each patient was also required Ͻ the Austin Research Institute, Melbourne) were subcloned into to have a WHO performance status of 2 and a life expectancy the antibody expression vectors pG1D102 and pKN100 (Med- of at least 3 months.
Load more

Recommended publications
  • 2007-AIBN-Annual-Report.Pdf
    AUSTRALIAN INSTITUTE FOR BIOENGINEERING AND NANOTECHNOLOGY (AIBN) ANNUAL REPORT 07 contents 2 DIRECTOR’S REPORT` 4 DYNAMIC RESEARCH ENVIRONMENT 6 INDUSTRY FOCUS 8 RESEARCH EXCELLENCE 10 BUILDING AUSTRALIA’S RESEARCH CAPABILITY 15 RESEARCH PROJECTS 16 MAMMALIAN CELL LINES AND STEM CELL BIOPROCESSES 17 BIOPROCESS TECHNOLOGY 17 SYSTEMS BIOTECHNOLOGY 18 TISSUE ENGINEERING AND MICROFLUIDICS 18 VASCULAR RESEARCH 19 STEM CELL ENGINEERING 20 BIOPOLYMER PROCESSING 21 NANOTOXICOLOGY, BIOMATERIALS AND TISSUE ENGINEERING 21 POLYMER CHEMISTRY 22 BIOMOLECULAR ENGINEERING 22 ADVANCED MATERIALS FROM COMPLEX POLYMER ARCHITECTURES 23 GENE AND DRUG DELIVERY RESEARCH 24 SINGLE MOLECULE NANOTECHNOLOGY 25 NANOTECHNOLOGY AND BIOMATERIALS 26 ENERGY INTERFACE ARCHITECTURE FOR POWER SYSTEMS 27 FUNCTIONAL NANOMATERIALS 27 COMPUTATIONAL BIO AND NANOTECHNOLOGY 28 AIBN GRADUATE PROGRAM 31 RESEARCH TRANSLATION AND COMMERCIALISATION 32 APPENDICES 33 RESEARCH GRANTS 36 AIBN PUBLICATIONS 41 AIBN STUDENTS 42 AIBN SEMINARS 44 AIBN MEDIA COVERAGE VICE-CHANCELLOR’S MESSAGE The University of Queensland’s Australian Institute for Bioengineering and Nanotechnology (AIBN) is rapidly gaining global traction by blending excellence in discovery with attention to the needs of industry and other end-users of research. Focussing on outcomes that will benefi t students, one quarter of whom are Professor Paul Greenfi eld AO human health and the environment, from overseas. In addition the AIBN VICE-CHANCELLOR AIBN scientists and engineers integrate has implemented new programs by THE UNIVERSITY OF QUEENSLAND the physical, chemical and biological which undergraduate students can sciences. They utilise some of Australia’s gain important laboratory experience newest and best bio infrastructure to that contributes toward their degrees. apply innovative ideas and techniques, This laboratory experience exposes and have the added advantage of the students to the leading edge of access to high-quality equipment and Australian bio/nano research, further people throughout UQ.
    [Show full text]
  • Reviewer Acknowledgments
    Reviewer Acknowledgments Margunn Aanestad Ajit Appari Wasana Bandara University of Oslo Dartmouth College Queensland University of Technology Oslo, Norway Hanover, New Hampshire Brisbane, Queensland, Australia Ahmed Abbasi Reina Arakji Youngsok Bang University of Wisconsin, Milwaukee City University of New York Baruch College KAIST Milwaukee, Wisconsin New York, New York Seoul, Korea Fran Ackerman Sinan Aral Ravi Bapna Strathclyde Business School New York University University of Minnesota Glasgow, Scotland New York, New York Minneapolis, Minnesota Alessandro Acquisti Alessandro Arbore James Barker Carnegie Mellon University Bocconi University Dalhousie University Pittsburgh, Pennsylvania Milano, Italy Halifax, Nova Scotia, Canada Shamel Addas Deborah Armstrong Reza Barkhi McGill University Florida State University Virginia Tech Montreal, Quebec, Canada Tallahassee, Florida Blacksburg, Virginia Gediminas Adomavicius Zaheeruddin Asif Henri Barki University of Minnesota Institute of Business Administration HEC Montreal Minneapolis, Minnesota Karachi, Pakistan Montreal, Quebec, Canada Maxim Afanasyev Jai Asundi Jordan Barlow Stanford University University of Texas, Dallas Brigham Young University Stanford, California Richardson, Texas Provo, Utah James Agarwal Michael Atwood Jack Baroudi University of Calgary Drexel University University of Delaware Calgary, Alberta, Canada Philadelphia, Pennsylvania Newark, Delaware Ritu Agarwal Neveen Awad Michael Barrett University of Maryland Wayne State University University of Cambridge Judge Business
    [Show full text]
  • Reviewer Acknowledgments, 2003
    Reviewer Acknowledgements We at the MIS Quarterly would like to thank the many excellent reviewers who have volunteered their time and expertise to make this an outstanding journal in the field. Their efforts make it possible for us to bring you quality articles in a timely manner. Ivan Aaen Deb Armstrong Michael Barrett Aalborg University University of Arkansas University of Cambridge Aalborg Öst, Denmark Fayetteville, AR 72701 Cambridge, United Kingdom Fran Ackermann Christopher Atkinson Kathryn M. Bartol University of Strathclyde Brunel University R. H. Smith School of Business Glasgow, Scotland Uxbridge, United Kingdom University of Maryland College Park, MD 20742 Dennis Adams Benoit Aubert University of Houston Hautes Etudes Commerciales Anitesh Barua Houston, TX 77204-6282 Montreal University of Texas at Austin Montreal, PQ, Canada Austin, TX 78712-1175 Gedas Adomavicius Carlson School of Management Rob Austin Richard Baskerville University of Minnesota Harvard Business School Georgia State University Minneapolis, MN 55455 Boston, MA 02163 Atlanta, GA 30302-4015 Ritu Agarwal Sulin Ba Genevieve Bassellier R. H. Smith School of Business University of Connecticut McGill University University of Maryland Storrs, CT 06269 Montreal, PQ, Canada College Park, MD 20742-1815 Sridhar Balasubramanian Irma Becca-Fernandez Manju K. Ahuja Kenan-Flagler Business School Florida International University Indiana University University of North Carolina University Park Campus Bloomington, IN 47405 Chapel Hill, NC 27599-3490 Miami, FL 33199 Jeffrey Allen
    [Show full text]
  • 2020 Annual Report PHOTOGRAPH CREDITS: Pp
    Response and Recovery 2020 Annual Report PHOTOGRAPH CREDITS: pp. 13/18/back cover, Brett Summerell; p. 19, CDC/Alissa Eckert, MSMI; Dan Higgins, MAMS. Contents Chairman’s 2019/2020 Bioplatforms report Highlights Australia 2 4 5 Bioplatforms Bioplatforms Feature network activities stories 6 7 8 Network National Collaboration LEADERSHIP access Initiatives and partnerships Bioplatforms Australia is committed to maintaining a high standard of governance and leadership. Strategic direction and operational oversight is provided by an independent Board of Directors and supported by an Executive Management Committee who advise on platform technologies and organisational initiatives. Board Members and Responsibilities Executive Management Committee 10 13 16 Bioplatforms Australia’s Directors offer a wealth of experience The Executive Management Committee manages and advises across scientific, business and government domains. on platform issues and operations. It is also responsible for Industry Capabilities BioCommons Each Director has responsibility for particular aspects of implementing strategic initiatives, including Commonwealth engagement network organisational strategy in addition to their fiduciary duties. funding agreements established with network partners. Dr Leslie Trudzik – Chairman Committee members are: Les is a founding Board Member of Bioplatforms Australia and Chair became Chairman in 2013. He is responsible for developing the Andrew Gilbert, Chief Executive, Bioplatforms Australia organisation’s performance and impact framework.
    [Show full text]
  • Honours Projects
    Honours Projects DR TRENT MUNRO / PROF. PETER GRAY Australian Institute for Bioengineering and Nanotechnology(AIBN) Phone: 07 3346 3947 Email: [email protected] Biopharmaceuticals and mammalian cell culture based biotechnology The acceptance of biopharmaceuticals as human therapeutics has been rapid, with global sales of such products now exceeding $US100 billion per annum. These sales are now growing at over 20% per annum, and there are many new biopharmaceuticals making up the potential product ‘pipelines’ of biotech and pharma companies. Of particular note is the rapid acceptance of human and humanised monoclonal antibodies as therapeutic agents. Antibodies, and the majority of other biopharmaceuticals, are large complex proteins that have to be produced by mammalian cell culture in order to have the correct post-translational modification they require for full biological activity. The Gray and Munro Labs are focused on engineering mammalian cells in order to improve their efficiency and utility in the production of complex proteins. The approaches used to gain greater understanding of such systems are also being applied to even more complex cells, viz the development of bioprocesses based on embryonic stem cells. Many of our research projects are collaborative, and often involve interactions with international biotech and pharma companies. Examples of available projects are: 1. Developing transient protein expression systems which will allow researchers to rapidly produce larger amounts of protein needed for initial characterisation and testing. 2. Developing high throughput approaches which allow the rapid selection of clones which stably express high levels of the desired biopharmaceutical. 3. Using modern ‘omics’ approaches to gain better understanding of cellular metabolism which will allow maximal protein expression by mammalian cell cultures.
    [Show full text]
  • Biotechnology
    School of Chemistry & Molecular Biosciences Faculty of Science BIOTECHNOLOGY Research Projects 2018 Honours Masters Res Ex Professional Doctorate Graduate Diploma Masters SCMB Biotechnology Research Projects 2018 | Industry Project Disclaimer “Every effort has been made to ensure the accuracy of information in this document at the time of publication. The authoritative source of program and course information is the UQ Courses and Programs website at www.uq.edu.au/study/. Where any conflict of information exists, the rules and associated course lists approved by the UQ Senate shall apply.” Last updated: 18 April 2018 2 SCMB Biotechnology Research Projects 2018 | Industry Project CONTENTS INDUSTRY PROJECTS Industry Contributors Organisation/Business Unit Page No. Professor Ross Barnard Director, Biotechnology Program 9 School of Chemistry & Molecular Biosciences Professor Peter Gray Australian Institute for Bioengineering and 10 Nanotechnology (AIBN) Professor Peer Schenk School of Biological Sciences 11 Professor Istvan Toth School of Chemistry & Molecular Biosciences / 12 TETRAQ Professor Matt Trau Australian Institute for Bioengineering and 13 Nanotechnology (AIBN) / School of Chemistry & Molecular Biosciences Advanced Water Management Centre 14 Dr Phil Bond Dr Liu Ye Professor Zhiguo Yuan Dr Bernadino Virdis Dr Damien Batstone Dr Jelena Radjenovic Dr Maria Jose Farre Dr Jens Kroemer Cook Australia Pty Ltd 15 Evolve Group 16 Fitgenes 17 QAAFI Honours Project/s Queensland Alliance for Agricultural and Food 18 Dr Michael Netzel Innovation (QAAFI) A/Prof Yasmina Sultanbawa Professor Neena Mitter Queensland Alliance for Agricultural and Food 19 Innovation (QAAFI) Dr Linda Lua Australian Institute for Bioengineering and 20 Nanotechnology (AIBN) Associate Professor Craig Williams School of Chemistry & Molecular Biosciences 21 GROUP PROFILES Group Name and Contributors Organisation/Business Unit Page No.
    [Show full text]
  • Annual Report 2010
    AIBN ANNUAL REPORT 2010 33 STUDENT EXPERIENCE 34 RHD report 36 Student profi le: Mirjana Dimitrijev Dwyer 37 Graduate profi le: Anthony Musumeci 38 2010/11 Summer internship 39 Occupational trainees 40 Research Higher Degree students 1 Vice-Chancellor’s message 41 SENIOR RESEARCHERS 2 Director’s message 42 Professor Peter Gray 4 Unique identity recognised in 43 Professor Kirill Alexandrov milestone review 44 Dr Bronwyn Battersby 6 AIBN benefi ts the economy 45 Associate Professor Idriss Blakey 7 RESEARCH ACHIEVEMENTS 46 Professor Julie Campbell 8 Integrated approach to improving 47 Professor Justin Cooper-White human health 48 Dr Annette Dexter 10 Latest in vaccine technology 49 Dr Krassen Dimitrov 12 Biologics research grows at AIBN 50 Professor John Drennan 14 Metabolic engineering through systems 51 Associate Professor Aijun Du and synthetic biology 52 Professor Peter Halley 16 Nano developments for diagnostic 53 Professor Mark Kendall advances 54 Professor Max Lu 18 Collaboration advances energy research 55 Associate Professor Stephen Mahler 20 Novel polymers and nanostructures for 56 Associate Professor Darren Martin new generation of products 57 Professor Anton Middelberg 22 Our vision 58 Professor Michael Monteiro 59 Professor Lars Nielsen 23 ENGAGEMENT 60 Dr Steven Reid 24 New Dow MOU 61 Professor Sean Smith 25 Biojet 62 Professor Matt Trau 26 Fabrication facilities open doors to 63 Associate Professor Christine Wells industry 64 Professor Andrew Whittaker 27 Continuing professional development 65 Associate Professor Ernst Wolvetang 28 Engaging through affi liates program 66 Professor Chengzhong (Michael) Yu 29 2010 HIGHLIGHTS 67 GRANTS 30 Fellowships 73 PUBLICATIONS 31 ARC achievement 32 Awards 79 AIBN SEMINARS 2010 VICE-CHANCELLOR’s MESSAGE AIBN offers proof that high-quality research generates excellent results for society, industry and the economy.
    [Show full text]
  • Meeting Registrants
    Meeting Registrants (as of 12/15/01) Count: 369 Michele E. M. Akoorie, Sch. of Mgmt., University of Waikato Gerald S. Albaum, University of New Mexico Poul Houman Andersen, Arhus School of Business Kartika D. Antono, Univ. of New South Wales Syed Tariq Anwar, West Texas A&M University Asli Arikan, Ohio State University Ilgaz Arikan, Ohio State University Jeffrey S. Arpan, University of South Carolina Sharif Nafe As-Saber, University of Tasmania Kaz Asakawa, Keio University Kevin Au, Chinese Univ. of Hong Kong Preet S. Aulakh, Temple University Catherine N. Axinn, Ohio State University Jay B. Barney, Ohio State University Jonathan Andrew Batten, Deakin University Schon L. Beechler, Columbia University - GSB John M. Beehler, Wichita State University Maryanne Benito, RMIT University Allan Bird, Univ. of Missouri, St. Louis Ingmar Bjorkman, Swedish School of Economics David J. Boggs, Saint Louis University Gordon Boyce, Victoria Univ. of Wellington Mary Yoko Brannen, San Jose State University Thomas L. Brewer, Journal of International Business Studies Charlotte Broaden, Southern New Hampshire University Jonathan L. Brookfield, University of Pennsylvania Brent M. Burmester, University of Auckland S. Tamer Cavusgil, Michigan State University Doren Chadee, University of Auckland Abhirup Chakrabarti, Nat'l Univ of Singapore Kwong Chan, Michigan State University Tsang-Sing Chan, Lingnan University Ranjan Chandran, Fox School Joseph Chiao-sen Chang, Tokyo University of Agriculture Shiou-Yu Chen, National Taiwan University Yao Chen, Yangzhou University Joseph Cheng, Univ. of Illinois, Urb.-Champaign Sylvie K. Chetty, Massey University Tailan Chi, Univ. of Illinois, Urb.-Champaign Dong-Sung Cho, Seoul National University Kang Rae Cho, Univ. of Colorado at Denver Soonkyoo Choe, Kookmin University Eun-Young Choi, Han Yang University Jaepil Choi, Hong Kong Univ.
    [Show full text]
  • Improving Culture Performance and Antibody Production in CHO Cell Culture Processes by Reducing the Warburg Effect
    Lars Nielsen ORCID iD: 0000-0001-8191-3511 Improving Culture Performance and Antibody Production in CHO Cell Culture Processes by Reducing the Warburg Effect Maria Buchsteiner1, Lake-Ee Quek1,2, Peter Gray1, Lars K. Nielsen1,3# 1 Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia 2 Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia 3 Novo Nordisk Foundation Center for Biosustainability, The Technical University of Denmark, Kgs Lyngby, DK-2800, Denmark #Corresponding author: Prof. Lars K. Nielsen, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia. Email: [email protected] Abstract Lactate is one of the key waste metabolites of mammalian cell culture. High lactate levels are caused by high aerobic glycolysis, also known as the Warburg effect, and are usually associated with adverse culture performance. Therefore, reducing lactate accumulation has been an ongoing challenge in cell culture development in order to improve growth, productivity and process robustness. The pyruvate dehydrogenase complex (PDC) plays a crucial role for the fate of pyruvate, as it converts pyruvate to acetyl-CoA. PDC activity can be indirectly increased by inhibiting the PDC inhibitor, pyruvate dehydrogenase kinase, using dichloroacetate (DCA); resulting in less pyruvate being available for lactate formation. Here, Chinese hamster ovary cells were cultivated either with 5 mM DCA or without
    [Show full text]
  • Conference Program
    Engineering Conferences International ECI Digital Archives Integrated Continuous Biomanufacturing IV Proceedings 10-6-2019 Conference Program Veena Warikoo Alois Jungbauer Jon Coffman Jason Walther Follow this and additional works at: https://dc.engconfintl.org/biomanufact_iv Part of the Engineering Commons Program Integrated Continuous Biomanufacturing IV October 6 – 10, 2019 Ocean Edge Resort Brewster (Cape Cod), Massachusetts Conference Chairs Veena Warikoo Roche, USA Alois Jungbauer BOKU, Austria Jon Coffman AstraZeneca, USA Jason Walther Sanofi, USA Engineering Conferences International 32 Broadway, Suite 314 - New York, NY 10004, USA www.engconfintl.org – [email protected] Ocean Edge Resort 2907 Main Street Brewster, MA 02631 Tel: 1-508-896-9000 Engineering Conferences International (ECI) is a not-for-profit global engineering conferences program, originally established in 1962, that provides opportunities for the exploration of problems and issues of concern to engineers and scientists from many disciplines. ECI BOARD MEMBERS Barry C. Buckland, President Mike Betenbaugh Joye Bramble Nick Clesceri Peter Gray Michael King Raymond McCabe Eugene Schaefer P. Somasundaran Chair of ECI Conferences Committee: Nick Clesceri ECI Technical Liaison for this conference: Mike Betenbaugh ECI Executive Director: Barbara K. Hickernell ECI Associate Director: Kevin M. Korpics ©Engineering Conferences International Steering Committee Konstantin Konstantinov (Codiak Biosciences) Charles L Cooney (Massachusetts Institute of Technology) Michael Betenbaugh
    [Show full text]
  • Cell Culture Engineering XIV
    Program Cell Culture Engineering XIV May 4 - 9, 2014 Fairmont Le Château Frontenac Quebec City, Canada Conference Chairs Amine Kamen McGill University, Canada Weichang Zhou WuXi AppTec Co., Ltd, China Engineering Conferences International 32 Broadway, Suite 314 - New York, NY 10004, USA Phone: 1 - 212 - 514 - 6760, Fax: 1 - 212 - 514 - 6030 www.engconfintl.org – [email protected] Fairmont Le Château Frontenac 1 rue des Carrières Québec City Quebec, Canada G1R 4P5 Toll Free: 1 866 540 4460 [email protected] TEL + 1 418 692 3861 FAX + 1 418 692 1751 Engineering Conferences International (ECI) is a not-for-profit global engineering conferences program, originally established in 1962, that provides opportunities for the exploration of problems and issues of concern to engineers and scientists from many disciplines. ECI BOARD MEMBERS Barry C. Buckland, President Mike Betenbaugh Peter Gray Michael King Raymond McCabe David Robinson William Sachs Eugene Schaefer P. Somasundaran Chair of ECI Conferences Committee: William Sachs ECI Technical Liaison for this conference: Mike Betenbaugh ECI Executive Director: Barbara K. Hickernell ECI Associate Director: Kevin M. Korpics ©Engineering Conferences International CCE Steering Committee Dana Andersen (Genentech, USA) John Aunins (Janis Biologics, USA) Mike Betenbaugh (Johns Hopkins University, USA) Barry Buckland (BiologicB LLC., USA) Jeff Chalmers (Ohio State University, USA) Matt Croughan (Amgen Bioprocessing Center / Keck Graduate Institute, USA) Peter Gray (University of Queensland, Australia) Carole Heath (Amgen, USA) Wei-Shou Hu (University of Minnesota, USA) Amine Kamen (McGill University, Canada) Konstantin Konstantinov (Genzyme, USA) Lynne Krummen (Genentech, USA) Kelvin Lee (University of Delaware, USA) Mark Leonard (Pfizer, USA) William Miller (Northwestern University, USA) Jamie Piret (University of British Columbia, Canada) Octavio Ramirez (UNAM, Mexico) Weichang Zhou (Wuxi App Tec Co., Ltd, China) Organization Committee Hal S.
    [Show full text]
  • Assessment of Health and Biomedical Science in Queensland
    Department of Science, Information Technology, Innovation and the Arts – Queensland Health Assessment of health and biomedical science in Queensland Professor Peter Andrews AO Professor John Shine AO Dr Debra Venables September 2014 Professor Peter Andrews AO This assessment of science and research activities, and co-Lead Author Queensland Government investment, in health and biomedical research institutes has been undertaken as part of the Peter Andrews is an eminent scientist and bio- Queensland Government’s examination of its science entrepreneur. He was appointed as Queensland’s first capability and investment, following the State government Chief Scientist in 2003, retiring in December 2010. election in March 2012. Professor Andrews completed his PhD in the This is the seventh in a series of audits of the Queensland pharmacological applications of quantum chemistry at Government’s scientific capability and investment, oversighted the University of Melbourne in 1969. He has since led by the Office of the Queensland Chief Scientist. multidisciplinary scientific teams at several Australian universities, and has been at the forefront of the The findings of this report are principally based on interviews development of the Australian biotechnology industry as conducted with representatives from Queensland’s health and a founder or board member of more than 10 scientific biomedical sector – including anecdotal evidence collected companies. during interviews. The findings are also informed by: Professor John Shine AO FAA • Data from the Queensland Government R&D Expenditure Report 2012-13, Health of Queensland Science (OQCS, co-Lead Author 2013), Queensland Life Sciences Report (OQCS, 2013). John Shine is a world-renowned Australian scientist. He • The Audit of Science Investment and Funding Programs was Executive Director of the Garvan Institute of Medical (Innovation & Science Development), DSITIA (May 2013).
    [Show full text]