Cancer Cell Therapy Markets

Table of Contents

1. Overview

• 1.1 About this Report
• 1.2 Scope of the Report
• 1.3 Objectives
• 1.4 Methodology
• 1.5 Executive Summary

2. Biology of Cellular Therapy for Cancer: Different Cell Types Deployed and Disease Areas Addressed

• 2.1 Components of the Hematopoietic System that can be Leveraged for Cancer Cellular Therapy
  • 2.1.1 Dendritic Cells
  • 2.1.2 Cytotoxic T Lymphocytes (CTLs)
  • 2.1.3 Natural Killer (NK) Cells
  • 2.1.4 Tumor Infiltrating Lymphocytes (TILs) also known as Lymphokine-activated Killers (LAKs)
  • 2.1.5 Hematopoietic Stem Cells (HSCs)
• 2.2 Adult Stem Cell-based Therapies (ASCs)
• 2.3 Stem Cell-based Cellular Therapies
  • 2.3.1 Effectiveness in Transplants of Peripheral Versus Bone Marrow Stem Cells
  • 2.3.2 What do HSCs do and what Factors are Involved in these Activities?
  • 2.3.3 Self-renewal of HSCs
  • 2.3.4 Differentiation of HSCs into Components of the Blood and Immune System
  • 2.3.5 Migration of HSCs Into and Out of Marrow and Tissues
  • 2.3.6 Apoptosis and Regulation of HSC Populations
• 2.4 Clinical Uses of HSC
  • 2.4.1 Leukemia and Lymphoma
  • 2.4.2 Inherited Blood Disorders
  • 2.4.3 HSC Rescue in Cancer Chemotherapy
  • 2.4.4 Graft-Versus-Tumor Treatment of Cancer
  • 2.4.5 Other Clinical Applications of HSCs
• 2.5 What are the Challenges and Barriers to the Development of New and Improved Treatments Using HSCs?
  • 2.5.1 Boosting the Numbers of HSCs
  • 2.5.2 The Immune System in Host, Graft and Pathogen Attacks
  • 2.5.3 Understanding the Differentiating Environment and Developmental Plasticity
• 2.6 Cancer Stem Cells
  • 2.6.1 The Microenvironment
  • 2.6.2 3-D Cultures and Spheres
  • 2.6.3 Targeted Therapies
• 2.7 Cellular Immunotherapy with DCs in Cancer
  • 2.7.1 Routes of DC Delivery
    • 2.7.1.1 Autologous Tumor Cell Vaccines and DC Therapy
    • 2.7.1.2 The Use of DCs for Cancer Vaccination
  • 2.7.2 Immune Response to Vaccination
  • 2.7.3 Clinical Studies with DCs
  • 2.7.4 Future of DC Therapy for Cancer
• 2.8 Tumor Immunotherapy Using DCs Pulsed with Tumor-derived Peptides
• 2.9 Recent Advances on the Use of Stem Cells in Cancer Therapies
• 2.10 Growth Factor Signaling Inhibitors
  • 2.10.1 EGFR Family Member Inhibitors
  • 2.10.2 Hedgehog, Wnt/β-Catenin and Notch Signaling Inhibitors
  • 2.10.3 Combination Therapies
  • 2.10.4 High-dose Cancer Therapy Plus HSCs
• 2.11 Cancer/Testis Antigens (CTAs): A Novel Cancer Marker?
• 2.12 Minimal Residual Disease (MRD) Post-Bone Marrow Transplantation for Hemato-Oncological Diseases
  • 2.12.1 Methods for Detection of MRD
    • 2.12.1.1 Nonmolecular Methods
    • 2.12.1.2 Immunophenotyping
    • 2.12.1.3 Restriction Fragment Length Polymorphism (RFLP)
    • 2.12.1.4 Southern Blotting for Detection of Clonal Genetic Markers
    • 2.12.1.5 PCR for Detection of Clonal Genetic Markers
    • 2.12.1.6 PCR of Minisatellite (VNTR) Sequences
    • 2.12.1.7 PCR of Microsatellite Sequences
    • 2.12.1.8 Y Chromosome-specific PCR
    • 2.12.1.9 PCR-Amelogenin: Improved Single-step PCR Assay for Gender Identification
    • 2.12.1.10 Quantitative PCR
    • 2.12.1.11 Two-color Fluorescence In situ Hybridization (FISH): BCR/ABL Fusion Gene Detection
    • 2.12.1.12 FISH in Sex-Mismatch Transplantation
• 2.13 Clinical Implications of Minimal Residual Disease
  • 2.13.1 Upfront Transplantation Decision Based on MRD Findings
  • 2.13.2 Prediction of Relapse Post-BMT
  • 2.13.3 Adoptive Immunotherapy for CML Patients Relapsing after BMT
  • 2.13.4 Mixed Allogeneic Chimerism as an Approach to Transplantation Tolerance
  • 2.13.5 BMT in Thalassemia and SAA and Detection of MRD
  • 2.13.6 Organ Transplantation
• 2.14 Genetic Engineering of Tumor Cells
  • 2.14.1 Hybridoma Process
  • 2.14.2 Hollow-fiber Perfusion
  • 2.14.3 Heat Shock Protein Technology
  • 2.14.4 Stem Cells Used as Platforms in Anticancer Therapies
  • 2.14.5 Stem Cell Transplantation in Cancer
  • 2.14.6 Bone Marrow Stem Cell Transplantation
  • 2.14.7 Cellular Immunotherapy Ex vivo Mobilization of Immune Cells
  • 2.14.8 Peripheral Blood Stem Cell Transplantation
  • 2.14.9 Autologous Stem Cell Transplantation
  • 2.14.10 Complications of Stem Cell Transplants in Cancer
  • 2.14.11 Umbilical Cord Blood Transplant for Leukemia
  • 2.14.12 MSC Transplantation in Cancer
  • 2.14.13 hESC-derived NK Cells for Treatment of Cancer Long-term Results of HSC Transplantation
• 2.15 The Human Immune System
• 2.16 Cell Therapy Commercialization

3. Current Status of Cellular Therapies for Cancer

• 3.1 Introduction to the Cancer Vaccine Space
  • 3.1.1 Tumor Cell Vaccines
  • 3.1.2 Antigen Vaccines
  • 3.1.3 DC Vaccines
  • 3.1.3.1 Dendritic/Tumor Cell Fusion
  • 3.1.3.2 Limitations of DC Vaccines for Cancer
  • 3.1.3.3 The Future of Cell Therapy with DCs
  • 3.1.4 Anti-Idiotype Vaccines
  • 3.1.5 Vector-based Vaccines
  • 3.1.6 Heat Shock Protein-based Vaccines
  • 3.1.7 Autologous Tumor Cell Vaccines
  • 3.1.8 Lymphocyte-based Cancer Therapies
    • 3.1.8.1 Adoptive Immunotherapy
    • 3.1.8.2 Rescue of CD8+ T Cells for Use in Tumor Immunotherapy
    • 3.1.8.3 Expansion of Antigen-specific CTLs
    • 3.1.8.4 Genetically Targeted T Cells for Treating B Cell Malignancies
    • 3.1.8.5 LAK Cell Therapy
    • 3.1.8.6 Tumor-infiltrating Lymphocyte (TIL) Therapy
• 3.2 Vaccines in Development
  • 3.2.1 GVAX Immunotherapies (Cell Genesys)
  • 3.2.2 Oncophage (Antigenics)
  • 3.2.3 Provenge (P-11) (Dendreon)
  • 3.2.4 Sipuleucel-T (Dendreon)
  • 3.2.5 DCVax® (Northwest Biotherapeutics)
  • 3.2.6 Stimuvax® (EMD Pharmaceuticals)
  • 3.2.7 JuvImmune™ (Juvaris BioTherapeutics)
  • 3.2.8 Allovectin-7® (Vical)
  • 3.2.9 BiovaxID (Biovest)
  • 3.2.10 BLP25 Liposome Vaccine (Merck & Co.)
  • 3.2.11 Cervarix (GlaxoSmithKline)
  • 3.2.12 Collidem® DC Vaccine (IDM Pharma)
  • 3.2.13 EP-2101 Lung Cancer Vaccine (IDM Pharma)
  • 3.2.14 FavId (Favrille)
• 3.3 Clinical Trials Pipeline for Various Types of Cellular Therapy for Cancer
• 3.4 Cancer Therapy Based on Natural Killer Cells
• 3.5 Cancer Stem Cells
• 3.6 ESC Vaccine for Prevention of Lung Cancer
• 3.7 Cell-based Therapies for Malignant Brain Tumors
  • 3.7.1 DC Therapy for Brain Tumors
  • 3.7.2 Targeting Stem Cells in Brain Tumors
  • 3.7.3 Conclusions
• 3.8 Vaccine for Non-Hodgkin' s Lymphoma
  • 3.8.1 Non-Hodgkin' s Lymphoma
  • 3.8.2 Monoclonal Antibody Treatment
  • 3.8.3 Development of Patient-specific Vaccine for NHL
  • 3.8.4 BiovaxID Active Immunotherapy
  • 3.8.5 BiovaxID Treatment and Production Process
  • 3.8.6 FavId
  • 3.8.7 MyVax
  • 3.8.8 Sector Competition
• 3.9 Bone Marrow Transplants
• 3.10 The Market Opportunity for the Use of Stem Cells in the Cancer Therapy Marketplace

4. Tumor Antigens, Cancer Vaccines and Cellular Therapy

• 4.1 Scope of this Chapter
• 4.2 Tumor Antigens and Classes
• 4.3 Classes of Cancer Vaccines Based on Tumor Antigens
  • 4.3.1 Antigen/Adjuvant Vaccines
  • 4.3.2 Whole Cell Tumor Vaccines
  • 4.3.3 DC Vaccines
  • 4.3.4 Viral Vectors and DNA Vaccines
  • 4.3.5 Idiotype Vaccines
• 4.4 Antigens that are Commonly Found in Cancer Vaccines under Investigation Today
  • 4.4.1 Treatment Vaccines
  • 4.4.2 Prevention Vaccines
• 4.5 Cancer Vaccines that have Reached Phase III Trials
• 4.6 Selected Companies in the Tumor Antigens and Vaccines Space with Novel Technology Platforms
  • 4.6.1 Antigenics
  • 4.6.2 AlphaVax
  • 4.6.3 Argonex
  • 4.6.4 Bavarian Nordic
  • 4.6.5 Biomira
  • 4.6.6 CancerVax Corp. (Micromet, Inc.)
  • 4.6.7 Corixa (Acquired by GlaxoSmithKline)
  • 4.6.8 CTL Immunotherapies
  • 4.6.9 Dendreon
  • 4.6.10 GenEra
  • 4.6.11 GeneMax Pharmaceuticals
  • 4.6.12 Genzyme Molecular Oncology
  • 4.6.13 IDM

5. Other Competing Antibody Technologies

• 5.1 Competition
• 5.2 Companies Developing Human Antibodies
• 5.3 Antibody Sequence Libraries
• 5.4 Recombinant DNA Sequences
• 5.5 Companies with Antibody Products in Clinical Trials
• 5.6 Immunoconjugates
• 5.7 Protein Products

6. The Future of Cell Therapy Against Cancer

• 6.1 Innovations in Cell-based Therapy of Cancer
  • 6.1.1 Cancer Therapy-based on NK-92 Cells
  • 6.1.2 Myoblast-mediated Gene Therapy
  • 6.1.3 Cancer Stem Cells
  • 6.1.4 MSCs for the Treatment of Gliomas

7. Government Regulation of Cell Therapy Products

• 7.1 Pharmaceutical Product Regulation
  • 7.1.1 Preclinical Phase
  • 7.1.2 Biologics
  • 7.1.3 Clinical Phase
• 7.2 New Drug Application (NDA) or Biologics License Application (BLA)
• 7.3 Fast-Track Review
• 7.4 Post-Approval Phase
• 7.5 Hatch-Waxman Act
• 7.6 Abbreviated New Drug Applications (ANDAs)
• 7.7 505(b)(2) Applications
• 7.8 Patent Term Restoration
• 7.9 ANDA and 505(b)(2) Applicant Challenges to Patents and Generic Exclusivity
• 7.10 Non-Patent Marketing Exclusivities
• 7.11 Orphan Drug Designation and Exclusivity
• 7.12 Cell Debris Therapy Ban

8. Companies involved in Cancer Cell Therapy

• 8.1 Companies Involved in Cell-based Cancer Therapy

9. Company Profiles

• 9.1 Accentia Biopharmaceuticals, Inc.
• 9.2 Antigenics, Inc.
• 9.3 Biomira, Inc.
• 9.4 Biovest International, Inc.
• 9.5 Cell Genesys, Inc.
• 9.6 Dendreon Corp.
• 9.7 EMD Serono (Parent Company is Merck KGaA, Darmstadt, Germany)
• 9.8 Favrille, Inc.
• 9.9 Genitope Corporation
• 9.10 Genzyme Molecular Oncology
• 9.11 GlaxoSmithKline
• 9.12 IDM Pharma, Inc.
• 9.13 Juvaris BioTherapeutics, Inc.
• 9.14 Medarex, Inc.
• 9.15 Merck & Co., Inc.
• 9.16 Micromet, Inc.
• 9.17 Northwest Biotherapeutics, Inc.
• 9.18 Titan Pharmaceuticals, Inc.
• 9.19 Vical, Inc.
• 9.20 Cyclacel Pharmaceuticals, Inc.

• Appendix I: List of Human Clusters of Differentiation (CD) Antigens
• Appendix II: Glossary of Terms in the Stem Cells Space
• Appendix III: Markers Commonly Used to Identify Stem Cells and to Characterize Differentiated Cell Types (Hematopoietic-focused)

INDEX OF FIGURES

• Figure 2.1: Autologous Process for Cancer Vaccination
• Figure 2.2: Patient Treatment Schedule for Second Line Caner Cell Therapy
• Figure 2.3: Cell Maturation Process
• Figure 2.4: CTL Cell Division
• Figure 2.5: Prostate Specific Membrane Antigen
• Figure 2.6: Exosomes
• Figure 2.7: Current End-user Utilization Category of CSCs
• Figure 2.8: Current End-user Utilization Category of Adult Stem Cells (ASCs)
• Figure 2.9: Current End-user Utilization Category of hESCs
• Figure 2.10: Current End-user Utilization Category of Human Cord Blood Stem Cells
• Figure 3.1: Cancer Vaccine Active Immune-Therapy Process
• Figure 3.2: Current End-user Utilization Category of CSCs

INDEX OF TABLES

• Table 2.1: TC Cell Activation
• Table 2.2: Innate Versus Adaptive Immunity
• Table 2.3: Proposed Cell-Surface Markers of Undifferentiated HSCs
• Table 3.1: Clinical Trials for Autologous Tumor Cell Vaccines
• Table 3.2: Pipeline of Cancer Vaccines
• Table 3.3: List of Cell Therapy Clinical Trials
• Table 3.4: Distribution of Adoptive Immunotherapy of Cancer Clinical Studies being Performed Worldwide
• Table 3.5: Clinical Studies Utilizing MSCs
• Table 3.6: Distribution of MSC-based Cancer Clinical Studies being Performed Worldwide
• Table 3.7: HSC-based Cancer Therapy
• Table 3.8: Distribution of HSC-based Cancer Clinical Studies Being Performed Worldwide
• Table 3.9: Characteristics of Different Stem Cell Types and Associated Market Opportunity
• Table 3.10: Segmentation of the Stem Cell Market by Type/Lineage of Stem Cell
• Table 4.1: Classes of Tumor Antigens
• Table 4.2: Cancer Vaccines in Phase III Clinical Trials
• Table 9.1: Cell Genesys Clinical Pipeline
• Table 9.2: Favrille Development Programs