ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS

The Sixth International Meeting of

Japanese Association for

Animal Cell Technology JAACT'93

JAACT'93 Organizing Committee Chairperson: Takeshi KOBAYASHI (School of Engineering, Nagoya University) Secretary General: Yasuo KITAGAWA (Nagoya University BioSciences Center) Organizing Boards: Shinji I1JIMA (School of Engineering, Nagoya University)

Tsukasa MATSUDA (School of Agriculture, Nagoya University) Tatsuo MURAMATSU (School of Agriculture, Nagoya University) Hiroyuki HONDA (School of Engineering, Nagoya University) Katsuzumi OKUMURA (Faculty of Bioresources, Mie University) Fumihiko HORIO (School of Agriculture, Nagoya University) Hiroaki ODA (School of Agriculture, Nagoya University) Kiyotaka HITOMI (School of Agriculture, Nagoya University) Kiyoshi MIKI (Nagoya University BioSciences Center)

Advisory Boards: Takeshi TOMITA (School of Agriculture, Nagoya University) Ryo NAKAMURA (School of Agriculture, Nagoya University) Atsushi KAKINUMA (Takeda Chemical Industries Ltd.) Shio MAKINO (School of Agriculture, Nagoya University) Norihiko TSUKAGOSHI (School of Agriculture, Nagoya University)

Program Committee Akio A MET ANI David BARNES Shun'ichi DOSAKO Nobuo FUJIYOSHI Shuichi HASHIZUME Hiroyoshi HOSHI Wei-Shou HU Koji IKURA Shuichi KAMINOGA W A Hermann KA TZINGER Kin'ichi KAWAMURA Anthony LUBINIECKI Yoji MITSUI Hiroki MURAKAMI Kazuo NAGAI TadaoOHNO Ryuzo SASAKI Kazuki SHINOHARA Sane taka SHIRAHA T A Yoshito SHIRAI YukioSOGO Takamoto SUZUKI Eiji SUZUKI

The University of Tokyo, Japan Oregon State University, U.S.A. Snow Brand Milk Products Co., Ltd., Japan Vessel Research Laboratory Co., Ltd., Japan Morinaga Institute of Biological Science, Japan Research Institute for Functional Peptides, Japan University of Minnesota, U.S.A. Kyoto Institute of Technology, Japan The University of Tokyo, Japan University of Agriculture and Forestry, Austria Komatsugawa Chemical Engineering Co., Ltd .. Japan SmithKline Beecham Pharmaceuticals, U.S.A. Tsukuba University, Japan Kyushu University, Japan Tokyo Institute of Technology, Japan Riken Gene Bank, Japan Kyoto University, Japan National Food Research Institute, Japan Kyushu University, Japan Kyushu Institute of Technology, Japan Snow Brand Milk Products Co., Ltd., Japan Kirin Brewery Co., Ltd., Japan The University of Tokyo, Japan

Animal Cell Technology: Basic & Applied Aspects

Volume 6

Proceedings of the Sixth International Meeting of the Japanese Association for Animal Cell Technology,

Nagoya, Japan, November 9- t 2, t 993

Edited by

T. KOBA Y ASH!

Y.KITAGAWA

and

K. OKUMURA

SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

A C.I.P. Catalogue record for this book is available from the Library of Congress

ISBN 978-94-010-4366-3 ISBN 978-94-011-0848-5 (eBook) DOI 10.1007/978978-94-011-0848-5

Printed on acid-free paper

All Rights Reserved © 1994 Springer Science+Business Media Dordrecht

Originally published by K1uwer Academic Publishers in 1994 No part of the material protected by this copyright notice may be reproduced or

utilized in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and

retrieval system, without written permission from the copyright owner.

Contents

Preface

Symposium 1

Process Validation for Virus Removal/Inactivation in the Bio-drug Purification Process

Evaluation of viral safety of biotechnology products derived from cell lines of human or animal origin

T. Hayakawa

Combination of virus removal and inactivation for optimization of recovery of protein

xv

T. Tsuboi and N. Yamamoto 9

Virus validation of therapeutic monoclonal antibodies (manuscript was not submitted) S. Mankarious

Strategy of virus removal/inactivation of plasma-derived products: Interest of nanofiltration as a new virus elimination method

T. Bumouf and M. Bumouf-Radosevich 17

Symposium 2

Insect Cell Culture and Baculovirus Expression

Development of a serum-free medium for growth of Trichoplusia ni (Tn 5B 1-4) cells and protein expression in free-suspension culture (manuscript was not submitted)

T. Gong

The NASA high-aspect ratio vessel (HARV): A novel bioreactor for insect-cell cultivation (manuscript was not submitted)

K. O'Connor

Perfusion of insect cell cultures: Application to recombinant protein production (manuscript was not submitted)

A. Bernard

Expression of the extracellular domain of the human growth hormone receptor gene by an insect-baculovirus system

Y. Ota, A. Asakura and M. Minami 29

Expression of recombinant receptors in insect cells B.C. Rooney, C.P.M. Woodcock and P.G. Strange 35

Production of a transmission blocking vaccine candidate of rodent malaria Plasmodium berghei using a baculovirus expression vector system

1. Kobayashi, H. Matsuoka, Y. Chinzei, R.E. Sinden and S. Miyajima 41

vi

Large-scale expression of heterologous proteins in baculovirus-infectedTrichoplusi ni cells and the effect of bC/-2 expression on cell viability and protein expression (manuscript was not submitted)

L. K. Overton

Symposium 3

Human Monoclonal Antibodies; Production, Characterization and Clinical Experience

Establishment of human B cell lines producing antigen-specific antibodies through scm mice reconstituted with human peripheral blood lymphocytes

N. Uchibayashi, A. Shino, T. Ochi, M. Okada, Y. Okubo and O. Shiho 47

Production of therapeutic human monoclonal antibodies by in vitro immunization of human splenocytes (manuscript was not submitted)

P. Boerner

Production of humanised monoclonal antibodies for in vivo imaging and therapy W.J. Harris 53

A humanized monoclonal antibody specific for human platelet GPIIb/I1Ia (manuscript was not submitted)

K. Kawamura

Humanized antibody to human FcRI in bi-specific antibody targeted therapy (manuscript was not submitted)

M.W. Fanger

Clinical results with humanized and human monoclonal antibodies lB. Cornett 63

Clinical applications of human monoclonal antibodies S. Hashizume, S. Sato, M. Kato, M. Kamei, K. Mochizuki, K. Kuroda, K. Kusakabe, K. Kanaya, K. Yasumoto, K. Nomoto and H. Murakami 75

Symposium 4

Transgenic Animals for Production of the Therapeutic Products

Large scale production of therapeutic proteins in livestock milk from concept to clinic (manuscript was not submitted) .

A. Colman

Lessons from HBY and EmMYC transgenic mice (manuscript was not submitted) K. Yamamura

Taking transgenic proteins to the clinic: Scientific and regulatory overview (manuscript was not submitted)

lA. Garaghty and R. Herndon

vii

Autocrine regulation of milk protein secretion CJ. Wilde, c.Y.P. Addey, AJ. Clark, S.E. Handel, M. A. Kerr, M. MacClenaghan, M.E. Rennison, J.P. Simons, M.D. Turner and R.D. Burgoyne 81

Therapeutic application of transgenic animals R. Kumar 87

FDA perspective on the use of transgenic animals in the manufacture of terapeutic products intended for human use: Safety concerns

J. Cavagnaro 95

Symposium 5

Cell Culture Technology in Tissue and Organ Engineering

Hepatocyte spheroid: Differentiated features and potential utilization for the bioreactor of artificial liver support

N. Koide, H. Hada, T. Yada, K. Kimata, T. Ogura, T. Matsushita, H. Ijima, K. Funatsu and T. Tsuji 99

Biomimetic design of glycoconjugates for hepatocyte and liver engineering (manuscript was not submitted)

T. Akaike

BAL commercialization: Points to consider along the way (manuscript was not submitted) B.P. Amiot

Microencapsulated islets as a bioartificial pancreas T. Takagi, H. Iwata, K. Kobayashi, T. Oka, H. Yang, H. Amemiya, T. Tuji and F. Ho 100

A novel three-dimensional long-term bone marrow bioreactor culture system T.-Y. Wang, A. Mantalaris and 1.H.D. Wu 115

Process technology in cellular and tissue engineering B.A. Pierson, S.H.Chao, M.Y. Peshwa and W.S. Hu 121

Symposium 6

Fish Cell Biotechnology

Fish IGF-I and IGF-II: Age-related and tissue-specific expression and transgenesis T.T. Chen, M. Shamblott and J.-K. Lu 127

From cell technology to embryo technology in MEDAKA (manuscript was not submitted) K.Ozato

Culture of zebra fish embryo cells for transgenic biotechnology (manuscript was not submitted)

viii

S. Bradford

Developing the Japanese MEDAKA as a new model (manuscript was not submitted) A. Shima

Inhibition of aquatic bimavirus replication process in fish cells by viral antisense RNA J.-L. Wu, S.-c. Long, S.-W. Yih, c.-y. Chang, C.-F. Liao and Y.-L. Hsu 137

Functional analysis of the homology and heterology promoters in fish-cultured cells T. Aoki, L. Fu, I. Hirono and M. Miyata 145

Derivation and characterization of cell cultures initiated from zebra fish embryo and adult tissues (manuscript was not submitted)

P. Collodi

Mini Symposium I

Novel Bioreactors for Animal Cell Culture

Dialysis perfusion systems for the production and retention of high-valued products from animal cells

B. Amos, M. AI-Rubeai and A.N. Emery 151

Design and performance of a packed bed bioreactor for the production of recombinant protein using serum-free medium (manuscript was not submitted)

G. Wang, W. Zhang, Y. Chen, C. Jacklin, H. Song, S. Gorfien and D. Freedman

Methods for animal cell immobilization using electrostatic droplet generation B. Bugarski and M.F.A. Goosen

Development of an immobilized cell reactor system for production purpose (manuscript was not submitted)

T. Matsumura, Y. Sawai, T. Ohno, J. Suzuki, H. Fujiwake, Y. Togawa, H. Hazama and Y. Ikegami

The use of stationary bed reactor for continuous and extended production of biomolecules (manuscript was not submitted)

A. Kadouri and D. Zipori

Using oxygen uptake rates to time infections in the baculovirus expression vector system

157

L.K. Nielsen, T.K.K. Wang, J. Power, S. Reid and P.F. Greenfield 161

The enhancement of oxygen transfer and cell growth by a moving-aeration bioreactor (manuscript was not submitted)

H.K. Kim, Y.S. Park, B.C. Jeon and H.Y. Lee

Mini Symposium II

Cell Culture Engineering for High Performance Production of Biologicals

Metabolic management of a hybridoma cell line (manuscript was not submitted) K. Murray, K. Gull and AJ. Dickson

On-line monitoring and control of glucose, glutamine, lactate and ammonium during a high-cell-density cultivation of hybridoma cells

ix

J.J. Van Der Pol, B. Joksch, U. Spohn, M. Biselli and C. Wandrey 167

Cultivation of hybridomas, human cancer and human primary cells using the miniaturized hollow fibre bioreactor TECNOMOUSE®

U. Marx, W. Merz, S. Koch, A. Nagel, M. SchiMke, P.M. Schlag, W. Liebrich, L. Ltibbe and R. von Baehr 171

Electrically controlled production of monoclonal antibody by immobilized hybridoma M. Aizawa, S. Ishihara, T. Haruyama, E. Kobatake and Y. Ikariyama 177

Effect of endogenous retrovirus production on hybridoma productivity L. Johnson, PJ. Phillips, C. Harbour and J.P. Barford 183

Effect of dissolved oxygen concentration on growth and production ofbiomaterials by animal cell culture

J. Wang, H. Honda, Y.S. Park, S. Iijima and T. Kobayashi 191

Enhanced productivity in insect cell culture by control of the chemical environment K.M. Radford, S. Reid and P.F. Greenfield 197

Energy balance and protein synthesis in hybridoma culture Y. Shirai, A. Kobayashi, M. Yamaguchi and K. Hashimoto 205

I. Expression of Recombinant Animal Genes in Cultured Cells

Application of fish cells immortalized by oncogenes - diagnostic method for the detection of fish iridovirus (Iridoviridae) by polymerase chain reaction

T. Tamai, K. Tujimura, H. Oda, N. Sato, S. Shirahata, S. Kimura, R. Kusuda and H. Murakami 213

Enhancement of cellular productivity by oncogene transfection S. Shirahata, K. Teruya, T. Yano, J. Watanabe, H. Tachibana, H. Ohashi and H. Murakami 219

Comparison of mutant ~-Iactoglobulin production between mammalian cell and yeast Y. Katakura, M. Totsuka, A. Ametani and S. Kaminogawa 225

Enhancement of 'Y-carboxylation of recombinant activated protein C by cell fusion Y. Takazawa, K. Wakabayashi, F. Miyagi, H. Takamatsu and S. Yokoyama 231

Modulation of oligosaccharide structure of a pro-urokinase derivative (pro-U~GSl) by culture conditions

S. Hosoi, K. Higo, S. Sugimoto, H. Miyaji, K. Karasawa, K. Yamaguchi, M. Hasegawa and T. Tamaoki 237

x

The analysis of antigen-antibody binding using anti-RNase A single chain Fv-3A21 E. Kobayashi, T. Kumamoto, T. Omasa, K. Fujiyama, S. Shioya and K. Suga 243

Enhanced transcriptional activity by modifying the chiken ovalbumin gene promoter in the oviduct cell of chickens

T. Muramatsu, H. Pak and J. Okumura 249

Expression of a foreign gene introduced into bovine embryos at early stages of development

T. Muramatsu, A. Nakamura and J. Okumura 255

Expression of milk protein-CAT chimeric genes in transfected bovine and mouse mammary epithelial cells

J.-Y. Ahn, K. Yamamoto, N. Aoki, T. Adachi, R. Nakamura and T. Matsuda 259

II. Establishment and Properties of Functional Cells

Differentiation and death of a small intestinal epithelial cell line, IEC-6 H.-K. Vi, S. Hachimura, A. Ametani and S. Kaminogawa 265

Establishment and characterization of as l-casein-specific T cell lines from milk -allergic patients

H. Nakajima, S. Hachimura, K. Honma, T. Katsuki, N. Shimojo, Y. Kohno, A. Ametani and S. Kaminogawa 273

Action of branched-chain amino acids on protein degradation in cultured muscle cells K. Yagasaki, Y. Kida, Y. Miura and R. Funabiki 279

Immortalization of human endothelial cells by temperature sensitive simian virus 40 H. Kirinaka, K. Miyake and S. Iijima 287

Establishment of hepatoblastoma cell line, HUH-6KK for production of biochemicals Z.-L. Kong 293

In vitro culture of primary B cells specific to a short peptide Y. Takahashi, A. Ametani, M. Totsuka and S. Kaminogawa 299

Leukemia inhibitory factor and related peptides regulate glial fibrillary acidic protein in serum-free mouse embryo (SFME) cells

K. Nishiyama, P. Collodi, L. Sun and D. Barnes 305

Factors affecting the induction of ovalbumin mRNA in primary cultures of oviductal cells in the chicken

T. Muramatsu, H. Hiramatsu and J. Okumura 311

Manipulation of chicken primordial germ cells for transgenic chicken J.Y. Han, D.S. Seo, R.N. Shoffner and K.S. Guise 317

III. Serum- and Protein-free Culture

Anchorage-dependent growth and recombinant protein production by chinese hamster ovary cells in serum-free medium

xi

P. J. Battista, M. L. Tilkins, D. W. Jayme and S. F. Gorfien 325

High cell density and seruin-free culture of hybridoma cells using fixed bed porosphere system

H. Watabe, Y. Fujino, K. Ono 331

Replacement of bovine insulin with recombinant long R 3 IGF-I in CHO cells V.P. Fung, J. Laity, S. Brown, L. Clark and J.N. Thomas 337

Serum-free medium for normal human melanocytes T. Ikeda, M. Sai, K. Fujiwara, T. Honjoh and S. Hashizume 345

IV. Enhancement of Productivity and Cost Performance for Producing Biochemicals

Intracellular analysis of a lymphoblastoid cell line using H-NMR PJ. Phillips, J.P. Barford, C. Harbour and P. Lundberg

Certified serum for productivity enhancement D. Yeoman

Recombinant antibody expression in a fixed bed perfusion system AJ. Racher and J.B. Griffiths

Cost effective high density mammalian cell culture T.C. Ripley, A. Nishi and E. Bognar

Continuous automated reconstitution of liquid media concentrates D.W. Jayme, J.M. Kubiak and PJ. Price

V. Cell Culture Engineering and High Density Culture

Relationship of inactivation techniques of the sera to cellular attachment on phema and polypropxlene surfaces ..

351

359

365

373

383

S.!. Gtirhan, N. Unal and M. Kiremitci 389

Establishment of a rat extracorporeal circulation system to estimate the performance of a hybrid artificial liver

H. Ijima, T. Matsushita, M. Taga, S. Wada, K. Hamazaki, N. Koide and K. Funatsu 395

Presumption of the concentration of several constituents in the culture broth of mouse­mouse hybridoma by near infrared reflectance spectroscopy

T. Yano and M. Harata 401

Enhancement of monoclonal antibody production related to metabolic behavior in high density hybridoma culture

T. Saito, A. Nishi and K. Murayama 407

xii

High density culture of rCHO cells using hollow fiber systems H. Kumazawa, Y. Tokushima, Y. Takenaka and N. Yamawaki 413

A hollow fiber bioreactor immobilizing hepatocyte spheroids rapidly formed by large-scale suspension culture

Y. Sakai and M. Suzuki 417

Effect of medium additives at AcNPV infection of insect cells on recombinamt ~­galactosidase production in batch and two-stage bioreactor systems

J.S. Kim, K.W. Lee, S.K. Kang, 1.M. Yang and I.S. Chung 423

On the enhancement of growth yields in hybridoma culture Y. Shirai, A. Kobayashi, M. Yamaguchi and K. Hashimoto 429

Production of rG-CSF by CHO cell in aggregate microbeads culture K. Nishii, X.-H. Xing, N. Shiragami and H. Unno 435

Perfusion culture using a macroporous microcarrier 1. Shirokaze, B. Fitzsimons, K. Konomoto and K. Sagara 441

High speed stirring culture using macroporous microcarrier K. Konomoto, B. Fitzsimons, 1. Shirokaze and K.Sagara 447

Cryopreservation of cell-laden collagen microspheres E.A. Bognar, A. Tung, A. Nishi, T.C. Ripley and A. Nadeau 453

A continuous cell centrifuge for lab scale perfusion processes of mammalian rells N. Chatzisavido, T. Bjorling, C. Fenge, S. Boork and E. Lindner-Olsson and S. Apelman 463

Polystyrene microcarriers coated with a combination of adhesion-promoting peptides J. Varani and W.J. Hillegas 469

VI. Cell Culture for Assessment of Physiologically Functional Substances

Chicken whole-embryo culture as a quick and convenient system for searching physiologically active compounds

R. Pinontoan,;1. Okumura and T. Muramatsu 475

Effect of fruit corqponents on the proliferation and antibody production of human-human hybridoma cellliJreS

Y. Fuke, Y. Ooishi and K. Shinohara 481

Induction of HMG-CoA reductase and malic enzyme gene expressions by polychlorinated biphenyls in rat hepatocytes cultured on EHS-gel, not on Type I collagen

H. Oda, Y. Suzuki, T. Shibata, Y. Hitomi and A. Yoshida 487

Effects of glycinin acidic:Ala subunit on insulin-involved cellular metabolism in rat adipocytes and 3T3-Ll cells

K. Ohkura, M. Mori, S. Yamakawa and S. Makino 491

Physiologically functional substances in shellfish toward several cultured mammalian cell lines

xiii

P. Pan and Z.-L. Kong 497

Purification and characterization of extracted abalone (Haliotis discus) bioactive protein F. Fang and Z.-L. Kong 503

Development of artificial skin using raft culture technique and its application to study the mechanism of oncogenesis

E.K. Yang, S. Park, D. Kwon, I. Kim, 1. Kim, I.S. Choe and J.K. Park 509

VII. Process Validation on Bio-drug Purification

The integrity test of virus removal membrane through gold particle method and liquid forward flow test method

T. Sato, T. Noda, S. Manabe, T. Tsuboi, S. Fujita and N. Yamamoto 517

Theoretical approach for integrity test of virus removal filter T. Noda, S. Manabe, T. Uragami, A. Higuchi and T. Sato 523

"The FDA quality/compliance continuum ... Where do cell culture and molecular biology products stand"

FJ. Manella 529

Removal of residual DNA in biological products by cuprammonium regenerated cellulose hollw fiber (BMWM)

S. Mizusawa, T. Sato, S. Fujita, R. Kobayashi, K. Misu, R. Homma and T. ~~ro 5TI

Removability and permeability of DNA in protein solution using BMMTM T. Hirasaki, K. Yamaguchi, A. Kono, T. Noda, T. Sugahara, N. Yamamoto and H. Murakami 543

VIII. Biological Properties of Proteins Produced by Animal Cells

Protectivein vivo effect against murine rickettsia infection by recombinant myeloperoxidase produced in CHO cells

P. Totte, N. Moguilevsky, N. Vachiery, C. Toumay, A. Bollen and 1. Werenne 549

A novel anti-tumorigenic protein specific to SV40- and human papilloma virus-transformed cells -the possible action mechanism-

Y. Kawamura, M. Manabe, T. Ookura and K. Kitta 555

Suppressive Iymphokines produced by CD8+ T cells K. Nishijima, T. Hisatsune, Y. Minai, K.Hirahara, M. Kohyama and S. Kaminogawa 561

Characterization of erythropoietin receptor on two neuronal cell lines S. Masuda, M. Nagao and R. Sasaki 567

xiv

Heterogeneity in light-chains of monoclonal antibodies produced by mouse hybridomas raised with NS-l myelomas

K. Inouye and N. Abe 575

Purification and characterization of two molecular forms of bovine complement factor H Y. Sakakibara, M. Suiko, P.H.P. Fernando, M. Miura and M.-C. Liu 581

Purification and characterization of growth and differentiation factors from human osteosarcoma cell line, OST-I-PF

K. Osawa, T. Shirai, M. Yanagawa, K. Yamada, K. Nishikawa and H. Tanaka 589

Protection against Cowdria ruminantium infection in mice with gamma interferon produced in animal cells

P. Toue, N. Vachiery, H. Heremans, A. Billiau and J. Werenne 595

A retrovirus-associated antigen expressed in human lung carcinoma S. Kawamoto, H. Tachibana, S. Shirahata and H. Murakami 601

Author Index 607

Subject Index 611

Preface

Animal cell technology is a newly growing discipline of cell biology which aims not only to understand structure, function and behavior of differentiated animal cells but also to uncover their ability useful for industrial purpose. The goal of animal cell technology includes clonal expansion of differentiated cells with useful ability, optimization of their culturing in industrial scale and modulation of their ability for production of drugs and monoclonal antibodies. When we regard the genetic information expressed during differentiation of fertilized eggs into over 200 different cell types of adult animal bodies as our natural resources, there is vast region to be explored by animal cell technologist. Most of the genetic information is expressed during limited period of animal development, and we might have many opportunity of utilizing such genetic information by cell technology. The subjects of animal cell technology are physical, physiological and genetical modulation of animal cells for full expression of their activity of our interest. Although conventional cell biologists might regard such effort to be far from the understanding of animal bodies, we believe that such cell engineering will also give more clear understanding of animal cells. The last five Annual Meetings of the Japanese Association for Animal Cell Technology (JAACT) had attracted increasing number of participants. At the Sixth Meeting (JAACT'93) held in Nagoya from November 9 through 12, 1993, we had more than 80 participants from outside of Japan and 230 from Japan. We have here completed the Meeting Proceedings which contains about 100 articles. We hope that this book will help worldwide researchers to envisage the present status and future trends in animal cell technology. The editors express their sincere gratitude to all researchers who joined the meeting, to the organizers of the Symposium Sessions, to members of the organizing committee who dedicated themselves in assuring the Meeting's success and the graduates students of Nagoya University who supported management of the Meeting. We also thank the Japanese Bioindustry Association and Nagoya Convention & Visitors Bureau for the financial support.

The Editors

xv