Cytokines, Chemokines, and Growth Factors- Key Targets for Immunotherapeutic Development - Market Research Reports

Contents:

1 Executive Summary 2 Opportunities for Drug Development 2.1. Introduction to Cytokine Networks, Chemokines, and Growth Factors 2.1.1. Cytokines 2.1.2. Cytokine Network 2.1.3. Chemokines 2.1.4. Autocrine, Paracrine, Intracrine, and Juxtacrine Growth Factors 2.1.5. Colony Stimulating Factors, Thymic Hormones, and Neurtotrophic Factors 2.2. Immunotherapeutics 2.2.1. Immunological Processes and Potential Therapeutic Strategies for Immunotherapy in Inflammation, Allergy, and Autoimmunity 2.2.2. Host Defense: Cancer and Infection 2.2.2.1. Hematopoiesis 2.2.2.2. Immune Cell Activation 2.3. Overview of Immunotherapeutic Strategies and Applied Technology 2.3.1. Cytokine Inhibitors and Immunomodulation 2.3.2. Key Companies Pursuing Cytokine Inhibitor Therapeutics 2.3.3. Companies Pursuing Strategies with Monoclonal Antibodies 2.3.4. Companies with Strategies to Use Polyclonal Antibodies and Intravenous Immunoglobulin (IVIG) 2.4. Cytokine-Based Gene Therapy 2.5. Drug Development Platforms 2.6. Biochips 2.7. The Power of Genomics 2.8. Immunodiagnostics 2.8.1. Cytokine Assays 2.8.2. World Health Organization (WHO) Cytokine Standardization 2.8.3. Cytokine Manufacturing 2.9. Referenced Links 3 Cytokine Classification and Nomenclature 3.1. Pleiotropic Nature of Cytokines 3.2. Cyokine Classification Systems 3.2.1. Cytokines Classed by Origin 3.2.2. Cytokines Classed by Main Functions 3.2.3. Cytokines Classed by Ligand-induced Receptor Signaling 3.2.4. Cytokines Classed by 3-Dimensional Structure 3.2.5. Cytokines Classed by Receptor Type 3.3. Cytokine Families 3.3.1. Interleukins 3.3.2. CD130 Ligand Family 3.3.3. Interleukin 10 Family 3.3.4. Interleukin 1 Ligand Family 3.3.5. Interleukin 1 Receptor Agonist (IL1ra) 3.3.6. Interferons 3.3.7. Tumor Necrosis Factors 3.3.8. Tumor Necrosis Factor Ligand Super Family 3.3.8.1. Nerve Growth Factor Family (Neurotrophins) 3.3.8.2. Other TNF Ligand Super Family Members 3.4. Cytokine Receptors 3.4.1. Cytokine Receptor Classification According to Domain Composition 3.4.2. Cytokine Receptor Families 3.4.3. Interleukin Receptors 3.4.3.1. Interleukin 1 Receptors IL-1 Receptors 3.4.3.2. Interleukin 2 Receptors IL-2 Receptors 3.4.3.3. Interleukin 3 Receptors IL-3 Receptors 3.4.3.4. Interleukin -4,-5,-6 and -7 Receptors, IL-4, -5, -6, and -7 R 3.4.3.5. Interleukin 10 IL-10 Family of Receptors 3.4.3.6. Interleukin 12 and 17 Receptors IL-12 and -17 R 3.4.3.7. Interleukin 13 Receptors IL-13 Receptor 3.4.4. Interferon Receptors 3.4.4.1. Tumor Necrosis Factor Receptors TNF Receptors 3.4.4.2. TNF/NGF Receptor Superfamily 3.5 Chemokines 3.5.1 Chemokines Classed by Origin 3.5.2 IUIS/WHO Subcommittee on Chemokine Nomenclature 3.5.3. Current Chemokine Descriptions 3.5.4 Chemokine Receptors 3.5.4.1 CXC Receptors 3.5.4.2 CC Receptors 3.5.4.3 Erythrocyte Chemokine Receptor 3.5.5 Chemokine Genomic Classifications 3.6 Growth Factors 3.6.1 Transforming Growth Factors TGF 3.6.2 Transforming Growth Factor TGF Super Family 3.6.2.1. Mullerian Inhibiting Substance MIS 3.6.2.2. Bone Morphogenetic Proteins BMP 1-15 3.6.2.3 Growth/Development Factors GDFs 3.6.2.4. Inhibin and Activin 3.6.2.5 Glial Derived Neurotrophic Factors GDNF Family 3.6.3 Transforming Growth Factor Receptors 3.6.3.1. TGF Binding Proteins 3.6.4. Ligands for the Immunoglobulin-Receptor Tyrosine Kinase (Ig-RTK) Superfamily 3.6.4.1. Granulocyte Colony Stimulating Factors G-CSF 3.6.4.2. Platelet Derived Growth Factors PGDF 3.6.4.3. Vascular Endothelial Growth Factors VEGF 3.6.4.4. Stem Cell Growth Factors SCGF 3.6.4.5. Fibroblast Growth Factor Family FGF 1-21 3.6.5. Ig-RTK Superfamily 3.6.5.1. CSF Receptors 3.6.5.2. Stem Cell Factor Receptor, C-KIT, SCFR, CD117 3.6.5.3 Platelet Derived Growth Factor PDGF Receptors 3.6.5.4. VEGF Receptor Family 3.6.5.5 FGF Receptors 3.6.6 Thrombopoietin TPO and Erythropoietin EPO 3.6.6.1. Thrombopoietin 3.6.6.2. Erythropoietin 3.6.6.3. TPO and EPO Receptors 3.6.7. Epidermal Growth Factor EGF Superfamily 3.6.7.1. Epidermal Growth Factor 3.6.7.2. Teratocarcinoma-Derived Growth Factor or Cripto Growth Factor CFC Family 3.6.7.3. Heregulin, Neuregulin and Other EGF Superfamily Members 3.6.7.4. EGF Receptors 3.6.7.5. Heregulin Receptors 3.7. Endothelial Cell Growth Factors 3.8. Insulin-like Growth Factors 3.8.1. IGF Receptors 3.8.2. IGF Binding Proteins 3.9. Macrophage Stimulating Protein 3.9.1. MSP Receptor (RON) 3.10. Pleiotrophin PTN and MidKine MK 3.10.1. Pleiotrophin - Heparin Affinity Regulatory Peptide 3.10.2. Midkine - A Structural Homologue of PTN 3.10.3. PTN and MK Receptors 3.11. Other Selected Growth Factors of Clinical Interest 3.12. Growth Factor Genomic Classifications 3.13. Virulence Factors (Virokines, Viral Cytokines) 3.14. Selected References 4 Cytokine-Associated Clinical Pathologies and Current Research I. Autoimmunity and Allergy 4.1. Autoimmune and Inflammatory Diseases 4.1.1. Rheumatic Autoimmune Diseases 4.1.1.1. Rheumatoid Arthritis RA 4.1.1.2. Cytokines in RA 4.1.1.3. Chemokines in RA 4.1.1.4. Growth Factors in RA 4.1.1.5. Cytokine Genes in RA 4.1.2. Juvenile Arthritis and Ankylosing Spondylitis 4.1.3. Systemic Lupus Erythematosus SLE 4.1.3.1. Major Cytokines in SLE: IL-4, IL-10, IL-12, IL-18, IFN-alpha, BAFF, CXCL13, VEGF 4.1.4. Sjogrens Syndrome SS 4.1.4.1. Major Cytokines in SS: IL-2, IL-6, IL-10, IL-13, IFN-gamma, BAFF, IP-10, CXCL13 4.1.5. Vasculitides 4.1.5.1. Major Cytokines in Vasculitis: IL-1beta, IL-1ra, IL-4, IL-5, IL-10, IL-15, CD40L, sTNFR, CTLA-4, IP-10, TGF-beta, VEGF 4.1.5.2. Idiopathic Thrombocytopenic Purpura 4.1.5.3. Autoimmune Hemolytic Anemia 4.1.5.4 Wegeners Granulomatosis 4.1.5.5. Giant Cell Arteritis 4.1.5.6. Kawasaki Disease 4.1.5.7. Churg-Strauss Syndrome 4.1.5.8 Bechets Disease 4. 2. Neurologic Autoimmune Diseases 4.2.1. Multiple Sclerosis MS 4.2.1.1. Major Cytokines in MS: IL-1beta, IL-6, IL-10, IL-12, IL-15, IL-23, TNF-alpha, IFN-alpha/beta, IFN-gamma, MIF, CCL3, CCL5, CCL10, CCL19, CCL21, GM-CSF, BDNF, VEGF 4.2.1.2. Chemokines in MS 4.2.1.3 Growth Factors in MS 4.2.1.4 Cytokine Genes in MS 4.2.2. Peripheral Neuropathy, Motor Neuron Disease and Neuropathic Pain 4.2.2.1. Major Cytokines in Neuropathy and ALS: IL-1beta, IL-3, IL-6, IL-12, LIF, TNF-alpha, NGF, NT-4, BDGF, GDNF, CNTF, HGF, IGF-1, CCL2, MCP-1 4.2.2.2. Amyotrophic Lateral Sclerosis 4.2.3. Myasthenia Gravis MG 4.2.3.1. Major Cytokines in MG: IL-1beta, IL-4, IL-5, IL-6, IL-12, IL-18, IFN-alpha, IFN-gamma, TNF-alpha, TGF-beta 4.2.4. Endocrinologic Autoimmune Diseases 4.2.4.1 Insulin-Dependent Diabetes Mellitus (IDDM, Type I) 4.2.4.2. Major Cytokines in IDDM: IL-1beta, IL-2, IL-4, IL-12, IL-18, IFN-gamma, MIP-1, IP-10, IGF-1, EGF, TGF-beta 4.2.5. Thyroiditis and Graves Disease 4.2.5.1. Major Cytokines in Graves Disease: IL-4, IL-6, IL-10, IL-12, IFN-alpha, TNF-alpha, MCP-1, GRO-alpha, CXCL9, CXCL10, VEGF, TGF-beta 4.2.6.1. Crohns Disease 4.2.6.2 Ulcerative Colitis 4.3. Dermatologic Autoimmune Diseases 4.3.1. Pemphigus and Psoriasis 4.3.1.1. Psoriasis and other Skin Disorders 4.4. Ophthalmic Autoimmune Diseases 4.4.1. Major Cytokines in Uveitis and Retinopathy: IL-1alpha, IL-10, IL-12, TNF-alpha, MIF, FKN, CCL2, CCL3, CCL5, CCL7, MIP-2, EDGF, VEGF, CTGF, PDGF, IGF-1, CNTF, TGF-beta 4.4.1.1. Uveitis 4.4.1.2. Retinopathy 4.5. Inflammatory Disease of the Heart 4.5.1. Major Cytokines in Myocarditis: IL-1alpha/beta, IL-6, IL-12, TNF-alpha, CD27L, CD30L, GM-CSF, MCP-1, VEGF 4.6. Inflammatory Disease of the Kidney 4.6.1. Major Cytokines in Nephritis: IL-1beta/IL-1R2, IL-6, sIL-6R, IL-10, IL-12, IL-18, TNF-alpha, TGF-beta, M-CSF, G-CSF, MIF, PDGF, MCP-1, Mig, IL-8 4.7. Allergic and Atopic Diseases 4.7.1. Major Cytokines in Dermatitis: IL-2, IL-4, IL-5, IL-13, IL-16, IL-17, IL-18, TNF-alpha, IFN-gamma, CCL2, CCL4, CCL17, CCL22, EDGF, NGF 4.7.2. Chemokines and Growth Factors in Dermatitis 4.7.3. Cytokine Genes in Dermatitis 4.8. Nasal and Ocular Allergy 4.8.1. Major Cytokines in Rhinosinusitis and Keratoconjunctivitis 4.9. Asthma and Bronchitis 4.9.1. Major Cytokines in Asthma: IL-4, IL-5, IL-9, IL-10, IL-12, IL-13, IL-25, IFN-gamma, TNF-alpha, TRAIL, TARC, Eotaxin, IP-10, GM-CSF, NGF, VEGF 4.10. Coeliac Disease and Food Allergy 4.10.1. Major Cytokines in Coeliac Disease CcD and Food Allergy: IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IFN-gamma, TNF-alpha, TGF-beta, IGF-1 4.10.1. Food Allergy 4.12. Cytokine References for Autoimmune and Allergic Diseases (2002-Present) 5 Cytokine-Associated Clinical Pathologies and Current Research II. Oncology 5.1. Immunotherapy with TGF-beta, TNF-alpha, IFN-gamma, GM-CSF, IL-2, IL-6 and IL-12 5.2. Brain Cancer 5.2.1. Major Cytokines in Brain Neoplasms: IFN-gamma, IL-2, IL-4, IL-6, IL-12, IL-13, IL-18, TRAIL, CXCL12, M-CSF, VEGF, PEDF, PDGF, CTGF, FGF, HGF, IGF-I, NGF, BDGF 5.2.2. Chemokines and Growth Factors in Brain Cancer 5.3. Endocrine Tumors 5.3.1. Pituitary Adenoma 5.3.2. Major Cytokines in PA and TC: IL-2, IL-6, IL-12, TNF-alpha, LIF, MIF, CXCL2, CXCL12, TGF-beta, Ang-2, VEGF, FGF-2, NGF, IGF-I, IGF-II, Activin, Leptin 5.4. Breast Cancer BC 5.4.1. Major Cytokines in Breast Cancer: IL-4, IL-8, IL-15, IL-18, IFN-beta, CXCL12, MCP-1, M-CSF, TRAIL, TGF-alpha, TGF-beta, Heregulin, Ataxin, Leptin, IGF-I, IGFBP-3, EGF, FGF-2, HGF, KGF, VEGF, Epo, Ang-2 5.4.2. Growth Factors in Breast Cancer 5.4.3. Cytokine Genes in Breast Cancer 5.4. Ovarian, Endometrial and Cervical Cancers 5.4.1. Major Cytokines in Gynecological Tumors: IL-1alpha, IL-1beta, IL-6, IL-18, IFN-gamma, TRAIL, CCL5, CCL18, CXCL8, CXCL12, TGF-alpha, TGF-beta, OSM, MIS, KITL, NRG, Amphiregulin, Endothelin-1, HIF-1alpha, HGF, KGF, FGF-2, FGF-10, VEGF, IGF-II 5.5. Prostate Cancer PC 5.5.1. Major Cytokines in Prostrate Cancer: IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-15, IFN-beta, TNF-alpha, TRAIL, RANKL, FasL, MIS, MIC-1, TGF-beta, NGF, NRG, EGF, HB-EGF, FGF-2, FGF-7, FGF-8, TSP-1, VEGF, IGF-I 5.6. Renal and Bladder Cancers 5.6.1. Bladder Cancer CB 5.6.2. Major Cytokines in Renal and Bladder Cancers: IL-2, IL-6, IL-10, IL-12, IFN-gamma, CD40L, RANTES, G-CSF, TGF-beta, MCP-1, IL-8, NGF, EGF, HIF-2alpha, IGF-I, IGFBP-3, FGF-2, VEGF 5.6.3. Renal Carcinoma 5.7. Enteric Neoplasia 5.7.1. Major Cytokines in Colon and Stomach Cancer: IL-1alpha, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, IFN-beta, IFN-gamma, TNF-alpha, TGF-alpha, TGF-beta, Flt3L, OX40L, TRAIL, MIF, G-CSF, EGF, VEGF, Ang-1, ET-1, IGF-I 5.8. Liver and Pancreatic Cancers 5.8.1. Major Cytokines in Hepatocellular Carcinoma: IL-1beta, IL-6, IL-8, IL-10, IL-22, IFN-alpha, IFN-beta, IFN-gamma, TNF-alpha, CCL3, CXCL3, TGF-beta, GM-CSF, HGF, HDGF, EGF, FGF-19, VEGF, Ang2, IGF-I, IGF-II 5.8.2. Major Cytokines in Pancreatic Cancer CP: IL-1beta, IL-4, IL-6, IL-8, IL-12, IL-18, TNF-alpha, GM-CSF, TGF-beta, TRAIL, HGF, HB-EGF, FGF-5, PTN, NGF, Flt-3L, Midkine, SCF, Amphiregulin, HIF-1alpha, VEGF, IGF-I 5.9. Skin Cancer 5.9.1. Major Cytokines in Melanoma MM and Squamous Cell Carcinoma SCC: IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, IL-24, IFN-alpha/beta, IFN-gamma, ISGF-3 ISGF-15, TNF-alpha, FasL, TRAIL, SCF, GRO-alpha, CCL5, CXCL1, CXCL12, M-CSF, GM-CSF, TGF-beta, FGF-2, VEGF, HGF, EGF, CTGF, alpha-MSH 5.9.2. Chemokines and Growth Factors in Malignant Melanoma MN and Squamous Cell Carcinoma SCC 5.10. Lung Cancer LC 5.10.1. Major Cytokines in Lung Cancer LC: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IL-18, IL-24, IFN-alpha, IFN-gamma, TNF-alpha, CD40L, FasL, TRAIL, MIF, MDC, SCF, CX3CL1, RANTES, IL-8, MCP-1, MIP-1, IP-10, TGF-beta, OSM, OX40L, GM-CSF, EGF, HGF, FGF-2, Ang-2, PTN, VEGF, IGF-I/II 5.10.2. Chemokines and Growth Factors in Lung Cancer LC 5.11. Leukemia and Lymphoma 5.11.1. Major Cytokines in Hematological Malignancies : IL-2, IL-3, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-alpha, IFN-gamma, TNF-alpha, FasL, TRAIL, TWEAK, Flt-3L, CD40L, G-CSF, GM-CSF, Epo, Tpo, OPG, RANKL, MCP, MIP-1alpha, IL-8, CCL17, CCL20, CCL22, CXCL6, CXCL12, CXCL13, CXCL16, TGF-beta, VEGF, HGF, FGF-2, FGF-6, IGF-I, Activin A, Endostatin 5.12. Transplant Rejection TR and Graft vs. Host Disease GHD 5.12.1. Major Cytokines in Transplant Rejection TR and Graft vs. Host Disease GHD: IL-1beta, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-15, IL-17, IL-18, IFN-gamma, c-KitL, CD40L, CD134L, B7L, FasL, TRAIL, TNF-alpha, MIP-1alpha, RANTES, IP-10, Mig, I-TAC, IL-8, CCL21, M-CSF, G-CSF, GM-CSF, Epo, TGF-beta, VEGF, FGF-1, FGF-2, PDGF-A, HGF 5.12.2. Chemokines and Growth Factors in TR and GVHD 5.12.3. Cytokine Genes in TR and GHVD 5.13. References for Cytokines in Cancer and Transplantation 6 Cytokine-Associated Clinical Pathologies and Current Research III. Infection and Wound Healing 6.1. Cytokines and the Host Response to Infection and Vaccines 6.2 Fungal and Parasitic Infections 6.2.1. Malaria and Plasmodium 6.2.2. Leishmania 6.2.3. Neuroinvasive Parasites 6.2.4. Other Parasites 6.2.5. Other Fungi and Yeast 6.3. Bacterial Infections 6.3.1. Tuberculosis and Mycobacteria 6.3.2. Gut Infection and Helicobacter pylori 6.3.4. Bacterial Pneumonia and Anthrax 6.3.5. Other Bacterial Cytokine Responses 6.4. Viral Infections 6.4.1. AIDS and Retroviruses 6.4.2. Hepatitis Viruses 6.4.3. Herpesviruses 6.4.4. West Nile Virus and Other Neurotrophic Viruses 6.4.5. SARS and Other Respiratory Viruses 6.4.6. Papillomavirus and Cervical Cancer 6.4.7. Other Viral Cytokine Responses 6.5. Cytokines in Wound Healing and Regeneration 6.5.1. Growth Factors in Wound Healing and Regeneration 6.6. Infections and Wound Healing References 7 Cytokine-Based and -Modifying Immunotherapeutic Biologicals, Drugs, Vaccines, and Gene Therapy 7.1. Roles of Cytokine Immunotherapy 7.1.1. Types of Immunotherapy and Cytokine Modifications 7.2. Cytokine Immunotherapy and Clinical Trials Overview 7.2.1. Tumor Necrosis Factor TNF 7.2.2.1. Enbrel Mediated Antagonism 7.2.2.2. Infliximab Another Anti TNF Alpha Humanized Chimeric Monoclonal 7.2.2 Modulation of Other TNF Family Members 7.2.3. Apoptosis Through TRAIL and FasL 7.2.4. Interferon IFN Family 7.2.4.1. Interferon Derivatives and Enhancers 7.2.5. Interferon beta 1 treatments for Multiple Sclerosis 7.2.6. Interleukin I IL-1 and IL-1Ra Market Opportunities 7.2.7. Interleukin 2 IL-2 and IL-2R (CD25) 7.2.8. Interleukin 3 IL-3/IL-3R 7.2.9. Interleukin IL-4/IL-4R 7.2.10. Interleukin 5 IL-5 7.2.11. Interleukin 6 IL-6 7.2.12. Interleukin 9 IL-9 7.2.13. Interleukin 10 IL-10 7.2.14. Interleukin 11 IL-11 7.2.15. Interleukin 12 IL-12 7.2.16. Interleukin 13 IL-13 7.2.17. Interleukin 15 IL-15 7.2.18. Interleukin 18 IL-18 7.2.19. Interleukins 20 and 21 IL-20 and IL-21 7.2.20. CD40/CD154 7.2.21. Leukemia Inhibitory Factor LIF 7.2.22. OX40L 7.2.23. Macrophage Migration Inhibitory Factor MIF 7.3. Chemokine Immunotherapy and Clinical Trials 7.3.1. CCR2 Antagonists 7.3.2. CCR3 Antagonists 7.3.3. CCR4 and CCR8 Antagonists 7.3.4. CCR5 7.3.6 CXCR Antagonists 7.3.7. IL-8 (CXCL8) Modulation 7.4. Growth Factor Immunotherapy and Clinical Trials 7.4.1 Colony Stimulating Factors (CSF) 7.4.2. Granulocyte Macrophase Stimulating Factor GM-CSF 7.5. Chemotherapeutics and Anti-inflammatory Drugs: Non-specific Cytokine Modulation 7.5.1. Drugs that Modulate Cytokine Production 7.5.2. Corticosteroids and Cytokines 7.6. Cytokine Gene Therapy 7.6.1. Clinical Trials in Progress 7.7. DNA vaccines and Cytokines 7.8. Growth Factor Immunotherapy and Clinical Trials 7.8.1. Transforming Growth Factor TGF 7.8.2. Bone Morphogenetic Protein BMP 7.8.3. Neutrophil Regeneration factors CSF 7.8.4. GM-CSF 7.8.5. Erythropoietin EPO 7.8.6. Thromobopoietin TPO 7.8.7. Epidermal Groth Factor EGF and EGFR- the HER System 7.8.8. Platelet Derived Growth Factor PDGF 7.8.9. Fibroblast Growth Factor FGF 7.8.10. Repifermin KGF-2 (FGF-7) 7.8.11. Connective Tissue Growth Factor CTGF 7.8.12. Pigment Epithelium Derived Factor PEDF 7.8.13. Vascular Endothelial Cell Growth Factor VEGF 7.8.14. Insulinlike Growth Factor IGF/IGF-1R 7.8.15. Myotrophin Dispute 7.8.16. Troponin I and AF-1 7.8.17. Ciliary Neurotrophic Factor CNTF 7.8.18. Prosaposin 7.8.19. Neural Growth Factor NGF and Small Molecule Neurotrophic Factors 7.8.20. Brain Derived Neurotrophic Growth Factor BDNF 7.8.21. Neurturin, Neublastin and GDNF 7.8.22. Gastrin 7.8.23. Thymosin 7.9. Indirect Cytokine Manipulation Strategies 7.9.1. Signal Transduction Pathways and Transcription Factors 7.9.2. Receptor Kinase RTKs 7.9.3. Mixed Lineage Kinase MLK 7.9.4. Phosphodiesterase Type 4 Enzyme PDE4 7.9.5. Ras/Raf 7.9.6. MAP Kinase MAPK and /MEK 7.9.7. Gene Regulating kinase JNK 7.9.8. Inosine Monophosphate Dehydrogenase IMPDH 7.9.9. Interleukin Beta Converting Enzyme ICE 7.9.10. NF-kappaB and IkappaB 7.9.11. Pre-Ligand Assembly Domain PLAD 7.9.12. HIF-1 alpha 7.9.13. Capases 7.9.14. Suppressors of Cytokine Signalling SOCS 7.9.15. NOTCH 7.10. Chemotherapeutics and Anti-inflammatory Drugs: Non-Specific Cytokine Modulation 7.10.1. Drugs that Modulate Cytokine Production 7.10.2. Dietary Supplements and Phytomedicines 7.10.3. Corticosteroids and Cytokines 7.10.4. Other Immunotherapeutic Interventions and Cytokine Manipulations 7.10.4.1. Intravenous Immuno Globulin IVIG therapy 7.10.4.2. BCG 7.10.5. Heparinase 7.10.6. Integrins 7.10.7. CD Antigens (Other than Cytokine Receptors) 7.11. Immunomodulation via Adoptive Transfer and Stem Cell Transplantation 7.11.1. Dendritic Cell/Tumor Cell Fusion Cancer Vaccine 7.11.2. Stem Cell and Bone Marrow Transplants 7.12. Antisense Cytokine Inhibitors 7.15. CpG Sequences 7.16. References 8 Cytokine Immunotherapeutics Companies: Profiles, Finances, and Partnerships Abbott Laboratories Abgenix, Inc. Advanced Biotherapy, Inc. Amarillo Biosciences, Inc. Amgen, Inc. Amrad Corporation, Ltd. AnGes MG, Inc. Applied Molecular Evolution, Inc. Avanir Pharmaceuticals, Inc. Avant Immunotherapeutics, Inc. Biogen, Inc. Biomira, Inc. BioVex, Ltd Boston Life Sciences, Inc. Cambridge Antibody Technology Group plc Celgene Corp. (Signal Pharmaceuticals) Celltech Group plc Centocor, Inc. (Johnson & Johnson) Cephalon, Inc. ChemoCentryx, Inc Chemokine Therapeutics Corp. Chiron Corp. Chugai Pharmaceutical Co. Ltd. Coley Pharmaceutical Group Corixa Corp. Deltagen, Inc. Enact Pharma plc Essex Bio-Technology, Ltd. Genaera Corp. Genentech, Inc. GeneTrol Biotherapeutics, Inc. Genmab A/S Genzyme Corp. Guilford Pharmaceuticals, Inc. Human Genome Sciences, Inc. ICOS Corporation ImClone Systems, Inc. Immuno-Designed Molecules, SA ImmunoGen, Inc. Immunomedics, Inc. Incyte Corporation Interleukin Genetics, Inc. Isis Pharmaceuticals, Inc. Ligand Pharmaceuticals, Inc Maxim Pharmaceuticals, Inc. Medarex, Inc. MedImmune, Inc. Millennium Pharmaceuticals, Inc. Onyx Pharmaceuticals, Inc Peregrine Pharmaceuticals, Inc. Protein Design Labs, Inc. Protherics plc Regeneron Pharmaceuticals, Inc. RegeneRx Biopharmaceuticals, Inc ReNeuron Holdings plc Repligen Corp. SangStat Medical Corp. Savient Pharmaceuticals, Inc. (Myelos Corp.) Schering-Plough Corp. SciClone Pharmaceuticals, Inc. Serono Inc. (Group) Sunesis Pharmaceuticals, Inc. Transgene S.A. Transition Therapeutics, Inc. Valentis Inc. Vertex Pharmaceuticals, Inc. Virax Holdings, Ltd. Xenova Group plc Yamanouchi Pharmaceutical Co. Ltd. ZymoGenetics, Inc.