Castilho Leda R., Moraes Angela Maria (Ed.) Animal Cell Technology: From Biopharmaceuticals to Gene Therapy

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Immortal cell lines 4, 150

Immortalization 4, 150, 443

Immunoadhesin 99

Immunoelectrophoresis 362

Immunogenicity 403, 404, 406

Immunoglobulin 138, 411, 413, 416, 422

In vitro assays

Comparison to in vivo cell growth 1, 10, 11

Cytotoxicity assays 10, 33–36

In vivo diagnosis 394, 396, 399

InductOs

393, 394

Industrial cell lines 30–31

Inoculum propagation 221

Insect cells 4, 6, 24, 25, 26, 31–33, 89, 91,

103–104, 112, 116, 118, 120, 122, 124,

135–136, 262, 422, 445, 448, 449, 455 459,

461, 462, 463, 464, 465, 466, 467, 469, 470

Insulin 118, 120, 121, 124, 125

Insulin 88, 119, 120, 121, 124, 125, 375, 383, 349,

366–367

Integrity of product 331

Intellectual property 373–388

Interference RNA 497–498

Interferons 2, 3, 6, 366–368, 375, 378, 379, 384,

390, 394, 402

Interleukin 99, 118, 119, 120, 485

Introduction of exogenous DNA 58

Calcium phosphate co-precipitation 58

DEAE-dextran 59

Electroporation 60

Lipofection 60

PEI 59

Intron A

402

Ion exchange chromatography 301, 310–313,

314, 319, 321, 323

Anion exchangers 311–312

Cation exchangers 311–312

Isoaspartate 138–139

Isoelectric focusing 301, 310 338, 339, 341, 362

Isoleucine 79, 87–89

Isozyme proﬁle 356

Karyotype 356

Keratinocytes 8, 486

Kidney 81, 96, 476

Kinetic analysis 182, 184, 185–200

Kogenate

3, 394, 398, 399

L mouse ﬁbroblasts 89

L929 cells 20

Labeling 404

Lactate 76, 78–87, 94–97, 101–103, 114, 116,

123, 184, 186, 188, 189, 201, 214, 496

Lactate dehydrogenase 78, 81–82, 188, 357

Laminin 27, 118, 125, 484

Langerhans islets 475

Lauric acid 93

LDH (see lactate dehydrogenase)

Lentivirus 9, 358, 492–493, 500

Lepidopteran 135–136

Leucine 79, 87–89, 113, 117

Leukemia 3, 500

Leukemia inhibitor factor (LIF) 485

Linoleic acid 91, 93–94, 113, 121

Linolenic acid 91, 93

Lipids 14, 15, 17, 75–76, 81–82, 91–93, 114, 116,

117, 118, 120, 125, 130, 436, 495

Lipofection 60, 500

Liposomes 9, 494–495

Liquid-liquid extraction 301, 303–304

Listeria noncytogenes 500

LLC-PK cells (porcine kidney cell) 81

Luveris

393, 394

Lymphoblastoid cell 20, 33, 90, 102

Lymphocyte 5, 31, 94, 119, 120, 375, 454, 482,

485

Lymphocyte choriomeningitis virus 357

Lysine 87–89, 113, 139, 142, 322

Macrophages 482, 497

Maillard reaction 139

Maintenance coefﬁcient 196, 204

Malate 79, 81–83, 101

Malate-aspartate shuttle 80–81, 95

Malic enzyme 81

Malignant transformation 19

Maltose 83, 116

Mannose 100, 116, 130–133, 135–138

Mannosidase 130–131, 137

Margaric acid 93

Mass balance 182

Master cell bank (MCB) 355–358

Mathematical model formulation 192–209

Models for animal cell cultivation 199–209

Mathematical model types 183–185

Non-Segregated 183, 185, 214–215

Non-structured 183, 192–214, 215–218

Population balance model 183, 215–218

Segregated 215–218

Structured 183, 185, 214–215

Mathematical model validation 213–214

MCB ( see master cell bank)

McCoy cells 86

MDBK cells 443

MDCK cells 4, 86–87, 90, 443

Membrane adsorption 321–322

Membrane ﬂuidity 93

Mesenchymal cells 479–481, 486

Metabolite monitoring 190, 267

Methionine 87–90, 113, 116

514 Animal Cell Technology

Methyl glyoxal 139

Methylation 134

MGH-U1 (human bladder cancer) cells 102

Microcarriers 27, 96, 229, 230, 443–446

Macroporous 229, 230

Manufacturers 230

Materials 230

Microporous 229, 230

Microﬁltration 301, 305

Micro-injection 375

Mitochondria 14, 15, 16, 23, 77, 80–82, 84, 89,

91–92, 95–99, 155, 159, 162, 167, 169, 171

Mitosis 17, 75, 147–149, 477

Modes of operation 234

Batch cultivation 235

Continuous cultivation 240

Continuous cultivation with cell retention

(perfusion) 242

Fed-batch cultivation 237

Molecular cloning 39

Molecular exclusion chromatography 301,

307–309, 323

Monitoring, process monitoring 184, 217, 259,

270

In situ 260

Off line 259, 263, 266, 267

Online 217, 260, 265, 266, 267

Real-time 259–260

Monoclonal antibodies 93, 139, 349, 355, 409–

433, 479, 487

Chimeric 419, 420, 421, 423

Human 419, 421–425

Humanized 410, 419, 420–421

Recombinant 418–425

Transgenic 421, 422

Monoclonal antibody production 425–430

In vivo 410, 425, 426

Transgenic animals 420

MRC-5 cells 4, 5, 20, 30, 31

Multiple sclerosis 391, 394

Multiplicity of infection 447, 451

Mutagenesis 492–493

Mutagenic activity 363–364

Mycobacterium leprae 498

Mycoplasma 29, 31, 121, 355–356, 360

Myeloma cell 3, 5, 20, 31, 83, 89–92, 103, 125,

358, 375, 409, 410, 414, 415, 416, 427

Human myeloma 410

Mylotarg

419

N-acetylglucosamine 100–101, 131

N-acetylglucosaminidase 136

N-acetylglucosamintransferase 137

N-acetylneuraminic acid 99–100

NAD 76, 79

Namalwa cells 2, 20, 124

Necrosis 23, 27, 151, colour plate/Fig. 7.3

Neulasta

403

Neupogen

402

Neural networks 270

Newcaste disease virus 500

NGF 119, 125

NIH 3T3 cells 20, 125

Non-viral vectors 9

Liposomes 9

Plasmid DNA 9, 50

Norwalk calcivirus 448

Norwalk virus 449

Notch 486

Novolin

402

NovoSeven

394, 399

NS0 cells 4, 20, 30, 31, 55, 427

Nucleases 494

Nucleotide sugars 130

Nutropin

402

Octanoic acid 93

OK cells (opossum kidney cell) 81

OKT3

418, 419, 426

Oleic acid 91, 93–94

Omalizumab 3

Omnitrope

367

Optimization 181, 182, 217, 426

Organ culture 34

Ornithine 85, 88–90

Ornithine transcarbamylase 500

Orthoclone

419

Osigraft

393, 394

Osmolality 24, 25–26, 29, 33, 111, 117, 123, 155

Osmolarity 96

Osteoblast 480, 484, 486

Ovitrelle

393, 394

Oxidative phosphorylation 79–80, 92

Oxoaldehydes 139

Oxygen 23, 24, 26, 27, 33, 77, 80, 101–103, 111,

116, 121, 123, 139, 141–142, 189–190, 246,

261, 263–265, 428, 442

Monitoring 259, 263–264

Control 264, 265, 269

Oxygen supply 26–27

Bubble free 26, 261, 263, 265

Gas bubbling 26, 27

Membrane diffusion 26, 263, 265

Pressure increases 26

Surface aeration 26, 27

Palmitic acid 93

Pancreas 476, 486

Panorex

419

Papillomavirus 435, 448, 449

Index 515

Parameter ﬁtting 182, 184, 185, 190, 192, 193,

201, 202, 204, 206, 208, 209–213

Parvovirus 441, 448, 449, 450, 453

Patentable materials 382–384

Patents 373, 374, 375, 402, 403

Grace period 378

Requirements for 376–382

Sufﬁciency of disclosure 381

PBM (see Mathematical model types)

pCO

(see Carbon dioxide, dissolved)

PDGF 118, 119, 120, 125

Peg-Intron

403

Pegylation 401, 403

Pentose phosphate pathway 77, 102–103

Peptide mapping 337, 340, 341

Per.C6 cells 4, 30, 31, 85

Perfusion cultivation 242

Permissible cells 436–437

pH 20, 24–26, 82, 85, 95–99, 101–104, 123, 139,

262–263, 362, 485, 496

Buffers 24, 25

Carbon dioxide 24, 25

Control 24, 262

Sodium bicarbonate 24, 25

Pharmacokinetics 365, 406

Phenylalanine 79, 88–89, 113

Phosphofructokinase 77–78, 81, 97, 100

Phospholipids 91, 93–94, 114

Phosphorylation 448

Plant cells 76, 137

Plastic bags 226–227, 444

Plate-and-frame membrane modules 286, 287

Pluronic

F68 94, 27, 120, 249

Pol gene 493

Poliovirus 443, 454, 500

Polyethylene glycol 303, 302, 314

Polyethyleneimine (PEI) 496

Polyomavirus 357, 449

Polystyrene 443, 445

Porcine parvovirus 449, 450, 453

Poxvirus 441, 500

Precipitation 300, 301, 302, 303, 304, 313, 314,

323

Primary cells 2, 4, 5, 10, 450

Primary cultures 4, 5, 17, 18, 19, 20, 119

Prions 121, 142, 357

Probe (see Sensor)

Process validation 129, 359

Product contaminants 329, 330, 331, 333,

335–336, 338, 340–341, 426

Product speciﬁcation 335–336

Productivity 252, 253, 255

Proline 79, 85, 88–90, 101, 113, 130, 133,

139–142

Prolyl-4-hydroxylase 142

Prophylaxis 489

Propidium iodide 157, 158

Prostaglandin 91, 93

Protease 21, 298, 300, 438

Protease inhibitors 119, 300

Protein C 140–141

Protein content 337

Protein extraction 298–300

Protein hydrolysates (see hydrolysates)

Protein precipitation 301–303

Precipitating agents 302

Salting-out 302

Protein purity ranges 297

Proteoglycans 21, 484, 496

Proteolysis 297, 300, 302, 362

Protropin

402

Puregon

393, 394

Puriﬁcation 295–324, 329, 330, 331, 335–336,

339, 340, 418, 423, 427, 445, 451

Purity 295–324, 330, 335, 336, 337, 338, 339, 342

Pyruvate 77–78, 80–83, 87, 91, 93–95, 103, 113,

115, 116, 118

Carboxylase 81, 83

Dehydrogenase 80–81

Kinase 77, 81

Phosphoenol carboxykinase 81

Quality assurance (QA) 350–351, 358–359

Quality control (QC)

Materials 331–333

Process 334–335

Product 335–342

Raptiva

419

Rebif

391, 394

Recombinant vaccines 436, 453

Regulatory agencies 389, 404

Regulatory aspects 329, 331, 349–372

Remicade

396, 401, 419

ReoPro

419

Reporter markers 64

Alkaline phosphatase (AP) 65

Beta-galactosidase (-gal) 64

Chloramphenicol acetyl transferase

(CAT) 64

Green ﬂuorescent protein (GFP) 65

Luciferase 65

Residual cellular DNA 361

Retractable housing 263

Retrovirus 5, 9, 31, 119, 358, 439, 440, 442,

492–493, 500

Reverse phase chromatography 313–314

Reverse transcriptase 358, 439, 493

Ribosome 15, 16, 17, 130, 133, 438

Rituxan

419

516 Animal Cell Technology

Roller bottle 444

Rotavirus 449, 454

S2 cells 32

Saccharomyces cerevisiae 83, 136, 500

Salmonella typhimurium 500

Salts 112, 113, 114, 117, 122, 124

Scale-up 250, 444

Schiff’s base 139

SCID mice- 422

SCID syndrome 9, 500

SDS-PAGE 301, 310, 338, 341, 362

Selection markers 61

Biochemical markers 61

Gene ampliﬁcation 61

Morphological changes 61

Semi-adherent cells 21

Semliki forest virus 500

Senescence 150

Sensors, principle of 263, 264, 266, 267, 417

Separation efﬁciency 274

Total separation efﬁciency 275, 276

Reduced total efﬁciency 276

Grade efﬁciency 277

Reduced grade efﬁciency 278

Sequon 130–133

Serine 85, 87, 89–90, 113, 130, 133–134

Serum 117–121

As a cell protecting agent 118, 121

Components 118

Functions 117

Risks associated to its use 121

Substitutes 27

Serum albumin 92, 125

Serum-free media 2, 4, 32, 85, 87, 92–94, 102,

111, 112, 117, 122–125, 300, 358, 501

Set-point 260, 269, 270

Sf-21 cells 449–451

Sf-9 cells 32, 89, 135, 449–451

Shear sensitivity 349, 445

Shear stress 154

SH-SY5Y cells 20

Sialic acid 100–101, 131, 135, 137–138

Sialylation 98–99, 103, 133–134, 136, 138

Sialyltransferases 136–137

Simian 40 virus 500

Simulect

3, 396, 419

Site-directed mutagenesis 406

Size exclusion chromatography (see molecular

exclusion chromatography)

Solid support (see substrata for cell adhesion)

Sp2/0 cells 4, 55, 83, 416, 417, 427

SP2Ag14/0 cells 416, 417, 427

Speciﬁc rate 182, 186–188, 261, 266

Death 186, 187, 203, 205, 211

Growth 183, 184, 187, 191, 193–196, 428

Product synthesis 181, 187, 188, 198, 199,

201, 205, 207, 208

Substrate consumption 188, 189, 190,

196–197, 204–205

Spheroids 34

Sphingolipids 91

Spodoptera frugiperda cells 32, 89, 135, 449, 451

Stability 330–333, 335, 337, 339, 423

Stearic acid 93

Stem cells 4, 7, 8, 475–487

Sterols 91

Stirring (see Agitation, Oxygen supply)

Substrata for cell adhesion 27

Substrate monitoring 190, 267

Succinamide 138

Sulfation 134

Superoxide dismutase 102

Suspended cells 21

SV-40 42, 45, 49, 51, 55, 449

Synagis

419

T antigen 136

T lymphocytes 418, 422, 425

TCA cycle 78–85, 87–92, 97, 99, 101, 103, 115

Temperature 26, 28, 101, 103, 110, 138–139, 259,

261–262, 355, 362, 485

Cell growth 26

Control 260, 261–262, 269

Cryopreservation 28

Upon thawing 28

Tenecteplase

394, 398, 406

Teratogenic activity 364

Teratomas 8

Terminal settling velocity 274, 280, 281

Tetrahydrofolate 89

TGF 119

Therapeutic enzymes 393, 394

Therapeutic proteins 389–408

Thermal degradation 86

Threonine 88–89, 101, 113, 133–134

Thrombospondin 484

Time of infection 447

Time-to-market 390, 402

Tissue engineering 8

Tissue plasminogen activator 2, 101, 133, 322

Toxicity 363–364, 492

Transamination 94

Transdifferentiation 475

Transesteriﬁcation 92

Transformed cells 19

Trastuzumab 3, 6

Trimera mouse 422

Trypsin 17, 21, 356–357

inhibitor 118

Index 517

trypsinization 22, 32, 33

Tryptophan 29, 88–89, 113

Tumor necrosis factor 99

Tumor-suppressing gene (p53) 501

TUNEL 156

U 266B1 cells 20

U937 cells 20

UDP-GlcNAc 100, 130, 138

UDP-GNAc 97, 99

Ultraﬁltration 301, 305–306

Ultrasonic separators 290

Umbilical cord 485–486

Urea 96

Vaccinia virus 500

Valine 88–89, 113

VEGF 485

Vectors (see Heterologous gene expression,

Non-viral vectors, Viral vectors)

Vero cells 2, 4, 20, 86, 443, 444, 445, 446, 447

Viral antigens 435

Viral vaccines 2, 435, 454

Viral vectors 9, 44–50, 435, 491–492, 498,

500–502

Virus 2, 4, 44–50, 121, 436–442, 140, 355–361,

371, 491–493, 500

Adsorption to cells 437

Genome structure 437–441

Infection 442

Internalization 437

Replication 436–437

Structure 436, 447

Virus-like particles (VLPs) 2, 7, 447, 453–455

Vitamin K 117, 141

Vitamins 113, 114, 117, 120, 122, 123, 125

Water quality 114–115

WCB (see Working cell bank)

WEHI 231 cells 20

Western blotting 362

WHO 350, 353–362

WI-38 cells 2, 4, 5, 102

Working cell bank (WCB) 355–357

Xenotransplants 475–476

Xigris

394, 402

Xolair

3, 396, 419

Xylose 135, 137

YAC 1 cells 20

Yield coefﬁcient 186, 188–189

Zenapax

396, 400, 419

Zevalin

419

518 Animal Cell Technology