Cancer Cell Therapy Markets

Table of Contents:

1. Overview 6
1.1 About this Report 6
1.2 Scope of the Report 7
1.3 Objectives 7
1.4 Methodology 7
1.5 Executive Summary 8
2. Biology of Cellular Therapy for Cancer: Different Cell Types Deployed and Disease Areas Addressed 11
2.1 Components of the Hematopoietic System that can be Leveraged for Cancer Cellular Therapy 11
2.1.1 Dendritic Cells 11
2.1.2 Cytotoxic T Lymphocytes (CTLs) 12
2.1.3 Natural Killer (NK) Cells 13
2.1.4 Tumor Infiltrating Lymphocytes (TILs) also known as Lymphokine-activated Killers (LAKs) 15
2.1.5 Hematopoietic Stem Cells (HSCs) 16
2.2 Adult Stem Cell-based Therapies (ASCs) 18
2.3 Stem Cell-based Cellular Therapies 21
2.3.1 Effectiveness in Transplants of Peripheral Versus Bone Marrow Stem Cells 22
2.3.2 What do HSCs do and what Factors are Involved in these Activities? 22
2.3.3 Self-renewal of HSCs 22
2.3.4 Differentiation of HSCs into Components of the Blood and Immune System 23
2.3.5 Migration of HSCs Into and Out of Marrow and Tissues 23
2.3.6 Apoptosis and Regulation of HSC Populations 23
2.4 Clinical Uses of HSC 24
2.4.1 Leukemia and Lymphoma 24
2.4.2 Inherited Blood Disorders 24
2.4.3 HSC Rescue in Cancer Chemotherapy 25
2.4.4 Graft-Versus-Tumor Treatment of Cancer 25
2.4.5 Other Clinical Applications of HSCs 25
2.5 What are the Challenges and Barriers to the Development of New and Improved Treatments Using HSCs? 26
2.5.1 Boosting the Numbers of HSCs 26
2.5.2 The Immune System in Host, Graft and Pathogen Attacks 26
2.5.3 Understanding the Differentiating Environment and Developmental Plasticity 27
2.6 Cancer Stem Cells 27
2.6.1 The Microenvironment 28
2.6.2 3-D Cultures and Spheres 29
2.6.3 Targeted Therapies 29
2.7 Cellular Immunotherapy with DCs in Cancer 29
2.7.1 Routes of DC Delivery 31
2.7.1.1 Autologous Tumor Cell Vaccines and DC Therapy 32
2.7.1.2 The Use of DCs for Cancer Vaccination 35
2.7.2 Immune Response to Vaccination 39
2.7.3 Clinical Studies with DCs 41
2.7.4 Future of DC Therapy for Cancer 42
2.8 Tumor Immunotherapy Using DCs Pulsed with Tumor-derived Peptides 43
2.9 Recent Advances on the Use of Stem Cells in Cancer Therapies 44
2.10 Growth Factor Signaling Inhibitors 45
2.10.1 EGFR Family Member Inhibitors 45
2.10.2 Hedgehog, Wnt/ß-Catenin and Notch Signaling Inhibitors 45
2.10.3 Combination Therapies 46
2.10.4 High-dose Cancer Therapy Plus HSCs 47
2.11 Cancer/Testis Antigens (CTAs): A Novel Cancer Marker? 48
2.12 Minimal Residual Disease (MRD) Post-Bone Marrow Transplantation for Hemato-Oncological Diseases 50
2.12.1 Methods for Detection of MRD 50
2.12.1.1 Nonmolecular Methods 50
2.12.1.2 Immunophenotyping 51
2.12.1.3 Restriction Fragment Length Polymorphism (RFLP) 51
2.12.1.4 Southern Blotting for Detection of Clonal Genetic Markers 51
2.12.1.5 PCR for Detection of Clonal Genetic Markers 52
2.12.1.6 PCR of Minisatellite (VNTR) Sequences 52
2.12.1.7 PCR of Microsatellite Sequences 52
2.12.1.8 Y Chromosome-specific PCR 52
2.12.1.9 PCR-Amelogenin: Improved Single-step PCR Assay for Gender Identification 53
2.12.1.10 Quantitative PCR 53
2.12.1.11 Two-color Fluorescence In situ Hybridization (FISH): BCR/ABL Fusion Gene Detection 53
2.12.1.12 FISH in Sex-Mismatch Transplantation 54
2.13 Clinical Implications of Minimal Residual Disease 54
2.13.1 Upfront Transplantation Decision Based on MRD Findings 54
2.13.2 Prediction of Relapse Post-BMT 55
2.13.3 Adoptive Immunotherapy for CML Patients Relapsing after BMT 55
2.13.4 Mixed Allogeneic Chimerism as an Approach to Transplantation Tolerance 56
2.13.5 BMT in Thalassemia and SAA and Detection of MRD 56
2.13.6 Organ Transplantation 57
2.14 Genetic Engineering of Tumor Cells 57
2.14.1 Hybridoma Process 57
2.14.2 Hollow-fiber Perfusion 58
2.14.3 Heat Shock Protein Technology 58
2.14.4 Stem Cells Used as Platforms in Anticancer Therapies 59
2.14.5 Stem Cell Transplantation in Cancer 61
2.14.6 Bone Marrow Stem Cell Transplantation 63
2.14.7 Cellular Immunotherapy Ex vivo Mobilization of Immune Cells 63
2.14.8 Peripheral Blood Stem Cell Transplantation 64
2.14.9 Autologous Stem Cell Transplantation 65
2.14.10 Complications of Stem Cell Transplants in Cancer 66
2.14.11 Umbilical Cord Blood Transplant for Leukemia 67
2.14.12 MSC Transplantation in Cancer 67
2.14.13 hESC-derived NK Cells for Treatment of Cancer Long-term Results of HSC Transplantation 67
2.15 The Human Immune System 68
2.16 Cell Therapy Commercialization 70
3. Current Status of Cellular Therapies for Cancer 71
3.1 Introduction to the Cancer Vaccine Space 73
3.1.1 Tumor Cell Vaccines 73
3.1.2 Antigen Vaccines 74
3.1.3 DC Vaccines 74
3.1.3.1 Dendritic/Tumor Cell Fusion 75
3.1.3.2 Limitations of DC Vaccines for Cancer 75
3.1.3.3 The Future of Cell Therapy with DCs 76
3.1.4 Anti-Idiotype Vaccines 76
3.1.5 Vector-based Vaccines 77
3.1.6 Heat Shock Protein-based Vaccines 77
3.1.7 Autologous Tumor Cell Vaccines 78
3.1.8 Lymphocyte-based Cancer Therapies 79
3.1.8.1 Adoptive Immunotherapy 79
3.1.8.2 Rescue of CD8+ T Cells for Use in Tumor Immunotherapy 79
3.1.8.3 Expansion of Antigen-specific CTLs 80
3.1.8.4 Genetically Targeted T Cells for Treating B Cell Malignancies 80
3.1.8.5 LAK Cell Therapy 81
3.1.8.6 Tumor-infiltrating Lymphocyte (TIL) Therapy 81
3.2 Vaccines in Development 81
3.2.1 GVAX Immunotherapies (Cell Genesys) 81
3.2.2 Oncophage (Antigenics) 81
3.2.3 Provenge (P-11) (Dendreon) 82
3.2.4 Sipuleucel-T (Dendreon) 82
3.2.5 DCVax® (Northwest Biotherapeutics) 82
3.2.6 Stimuvax® (EMD Pharmaceuticals) 82
3.2.7 JuvImmune™ (Juvaris BioTherapeutics) 83
3.2.8 Allovectin-7® (Vical) 83
3.2.9 BiovaxID (Biovest) 83
3.2.10 BLP25 Liposome Vaccine (Merck & Co.) 84
3.2.11 Cervarix (GlaxoSmithKline) 84
3.2.12 Collidem® DC Vaccine (IDM Pharma) 84
3.2.13 EP-2101 Lung Cancer Vaccine (IDM Pharma) 84
3.2.14 FavId (Favrille) 85
3.3 Clinical Trials Pipeline for Various Types of Cellular Therapy for Cancer 90
3.4 Cancer Therapy Based on Natural Killer Cells 177
3.5 Cancer Stem Cells 178
3.6 ESC Vaccine for Prevention of Lung Cancer 179
3.7 Cell-based Therapies for Malignant Brain Tumors 179
3.7.1 DC Therapy for Brain Tumors 179
3.7.2 Targeting Stem Cells in Brain Tumors 179
3.7.3 Conclusions 180
3.8 Vaccine for Non-Hodgkin's Lymphoma 180
3.8.1 Non-Hodgkin's Lymphoma 180
3.8.2 Monoclonal Antibody Treatment 181
3.8.3 Development of Patient-specific Vaccine for NHL 181
3.8.4 BiovaxID Active Immunotherapy 182
3.8.5 BiovaxID Treatment and Production Process 182
3.8.6 FavId 183
3.8.7 MyVax 183
3.8.8 Sector Competition 183
3.9 Bone Marrow Transplants 184
3.10 The Market Opportunity for the Use of Stem Cells in the Cancer Therapy Marketplace 184
4. Tumor Antigens, Cancer Vaccines and Cellular Therapy 187
4.1 Scope of this Chapter 187
4.2 Tumor Antigens and Classes 187
4.3 Classes of Cancer Vaccines Based on Tumor Antigens 188
4.3.1 Antigen/Adjuvant Vaccines 188
4.3.2 Whole Cell Tumor Vaccines 188
4.3.3 DC Vaccines 188
4.3.4 Viral Vectors and DNA Vaccines 188
4.3.5 Idiotype Vaccines 188
4.4 Antigens that are Commonly Found in Cancer Vaccines under Investigation Today 188
4.4.1 Treatment Vaccines 188
4.4.2 Prevention Vaccines 189
4.5 Cancer Vaccines that have Reached Phase III Trials 190
4.6 Selected Companies in the Tumor Antigens and Vaccines Space with Novel Technology Platforms 193
4.6.1 Antigenics 193
4.6.2 AlphaVax 193
4.6.3 Argonex 193
4.6.4 Bavarian Nordic 193
4.6.5 Biomira 193
4.6.6 CancerVax Corp. (Micromet, Inc.) 194
4.6.7 Corixa (Acquired by GlaxoSmithKline) 194
4.6.8 CTL Immunotherapies 194
4.6.9 Dendreon 194
4.6.10 GenEra 194
4.6.11 GeneMax Pharmaceuticals 194
4.6.12 Genzyme Molecular Oncology 194
4.6.13 IDM 195
5. Other Competing Antibody Technologies 196
5.1 Competition 196
5.2 Companies Developing Human Antibodies 196
5.3 Antibody Sequence Libraries 196
5.4 Recombinant DNA Sequences 196
5.5 Companies with Antibody Products in Clinical Trials 197
5.6 Immunoconjugates 197
5.7 Protein Products 197
6. The Future of Cell Therapy Against Cancer 198
6.1 Innovations in Cell-based Therapy of Cancer 198
6.1.1 Cancer Therapy-based on NK-92 Cells 198
6.1.2 Myoblast-mediated Gene Therapy 198
6.1.3 Cancer Stem Cells 199
6.1.4 MSCs for the Treatment of Gliomas 199
7. Government Regulation of Cell Therapy Products 201
7.1 Pharmaceutical Product Regulation 201
7.1.1 Preclinical Phase 201
7.1.2 Biologics 202
7.1.3 Clinical Phase 202
7.2 New Drug Application (NDA) or Biologics License Application (BLA) 203
7.3 Fast-Track Review 203
7.4 Post-Approval Phase 204
7.5 Hatch-Waxman Act 205
7.6 Abbreviated New Drug Applications (ANDAs) 205
7.7 505(b)(2) Applications 205
7.8 Patent Term Restoration 205
7.9 ANDA and 505(b)(2) Applicant Challenges to Patents and Generic Exclusivity 206
7.10 Non-Patent Marketing Exclusivities 206
7.11 Orphan Drug Designation and Exclusivity 207
7.12 Cell Debris Therapy Ban 207
8. Companies involved in Cancer Cell Therapy 208
8.1 Companies Involved in Cell-based Cancer Therapy 208
9. Company Profiles 211
9.1 Accentia Biopharmaceuticals, Inc. 211
9.2 Antigenics, Inc. 211
9.3 Biomira, Inc. 216
9.4 Biovest International, Inc. 220
9.5 Cell Genesys, Inc. 221
9.6 Dendreon Corp. 229
9.7 EMD Serono (Parent Company is Merck KGaA, Darmstadt, Germany) 233
9.8 Favrille, Inc. 235
9.9 Genitope Corporation 239
9.10 Genzyme Molecular Oncology 242
9.11 GlaxoSmithKline 242
9.12 IDM Pharma, Inc. 243
9.13 Juvaris BioTherapeutics, Inc. 247
9.14 Medarex, Inc. 251
9.15 Merck & Co., Inc. 252
9.16 Micromet, Inc. 252
9.17 Northwest Biotherapeutics, Inc. 255
9.18 Titan Pharmaceuticals, Inc. 259
9.19 Vical, Inc. 263
9.20 Cyclacel Pharmaceuticals, Inc. 264
Appendix I: List of Human Clusters of Differentiation (CD) Antigens 268
Appendix II: Glossary of Terms in the Stem Cells Space 274
Appendix III: Markers Commonly Used to Identify Stem Cells and to Characterize Differentiated Cell Types (Hematopoietic-focused) 284
INDEX OF FIGURES
Figure 2.1: Autologous Process for Cancer Vaccination 35
Figure 2.2: Patient Treatment Schedule for Second Line Caner Cell Therapy 36
Figure 2.3: Cell Maturation Process 37
Figure 2.4: CTL Cell Division 37
Figure 2.5: Prostate Specific Membrane Antigen 38
Figure 2.6: Exosomes 39
Figure 2.7: Current End-user Utilization Category of CSCs 59
Figure 2.8: Current End-user Utilization Category of Adult Stem Cells (ASCs) 60
Figure 2.9: Current End-user Utilization Category of hESCs 60
Figure 2.10: Current End-user Utilization Category of Human Cord Blood Stem Cells 60
Figure 3.1: Cancer Vaccine Active Immune-Therapy Process 73
Figure 3.2: Current End-user Utilization Category of CSCs 178
INDEX OF TABLES
Table 2.1: TC Cell Activation 13
Table 2.2: Innate Versus Adaptive Immunity 15
Table 2.3: Proposed Cell-Surface Markers of Undifferentiated HSCs 17
Table 3.1: Clinical Trials for Autologous Tumor Cell Vaccines 78
Table 3.2: Pipeline of Cancer Vaccines 86
Table 3.3: List of Cell Therapy Clinical Trials 90
Table 3.4: Distribution of Adoptive Immunotherapy of Cancer Clinical Studies being Performed Worldwide 104
Table 3.5: Clinical Studies Utilizing MSCs 105
Table 3.6: Distribution of MSC-based Cancer Clinical Studies being Performed Worldwide 107
Table 3.7: HSC-based Cancer Therapy 108
Table 3.8: Distribution of HSC-based Cancer Clinical Studies Being Performed Worldwide 177
Table 3.9: Characteristics of Different Stem Cell Types and Associated Market Opportunity 185
Table 3.10: Segmentation of the Stem Cell Market by Type/Lineage of Stem Cell 186
Table 4.1: Classes of Tumor Antigens 187
Table 4.2: Cancer Vaccines in Phase III Clinical Trials 190
Table 9.1: Cell Genesys Clinical Pipeline 222
Table 9.2: Favrille Development Programs 236