Global Cancer Immunotoxins Market & Clinical Pipeline Insight 2020
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Immunotoxins are new generation chemotherapeutic agents innovated to include the specificity of monoclonal antibody and cytotoxicity of toxins extracted from plant or bacterial source. The targeting moiety carries the specificity of the antibody and is directed to the target where it either binds to the cell surface antigen, receptor or the ligand of the targeted disease. Cytotoxicity is mediated by the protein toxins, which maybe protein at times.
The cytotoxic part may comprise of any molecule which has the capability to induce cell death either by interfering with the cell machinery, modifying cell membrane, or by induction of apoptotic pathways. The cytotoxicity thus successfully delivered either to cytoplasm or the ribosomes of the target cell may be lethal to the cell.
During its ignition era, immunotoxins basically comprised of monoclonal antibodies (MAb) or growth factors chemically conjugated to protein toxins by the formation of the disulphide bonds. These molecules contained full length protein toxins are were not that cell specific. With progress in the research and technology, second generation immunotoxins made an entry. They were modulated in a way to remove the toxin mediated cell binding and spare the normal cells from cytotoxicity. The immunotoxins of this generation contained full length Immunoglobulin (IgG) bound to the toxic moiety.
The entry of third generation was marked by coming of recombinant technology which was targeted to remove the immunogenicity by shifting from murine origin immunoglobulins to humanized recombinant IgGs. The molecules of this generation thus formed consisted of fragments of variable domain (Fv) conjugated to IgG. Thus, created immunotoxins had excellent activity, specificity, better penetration and less immunogenicity.
Immunotoxins continue to be actively investigated as viable alternatives to conventional therapies for a variety of diseases. An array of different recombinant, antibody formats are now available for use in immunotoxins. While these design changes have improved the overall in vitro and preclinical in vivo efficacy of immunotoxins, increased potency does not address either of the two major concerns for drugs of this type: immunogenicity and toxicity.
In the past three to four decades, a wide variety of immunotoxins have been tested against a wide variety of malignancies in cell culture, in animal models, and in patients. The most useful of these agents appear to be the relatively small recombinant fusion toxins that contain either growth factor or Fv fragments as ligands. The most sensitive diseases appear to be hematologic malignancies. Future development will need to address combinations of immunotoxins with other anticancer therapies in order to overcome problems of tumor penetration, toxicity, and immunogenicity.
After many years of pre-clinical development, there has been a recent burst in the number of clinical trials using antibodies or antibody fragments to target potent cytotoxic molecules to cancer cells. Several of these trials have shown impressive clinical responses indicating that we are at the beginning of a new and exciting phase of cancer treatment. Additional studies are now required to define the optimal dose, schedule, and combinations for specific malignancies. Also several problems have been identified. One of these is immunogenicity, which may be solved by removing B and T cell epitopes. Another is likely to be drug and toxin resistance. Never the less we expect this new approach is likely to have a major impact in cancer treatment.
“Global Cancer Immunotoxins Market & Clinical Pipeline Insight 2020” Report Highlights:
Immunotoxins are new generation chemotherapeutic agents innovated to include the specificity of monoclonal antibody and cytotoxicity of toxins extracted from plant or bacterial source. The targeting moiety carries the specificity of the antibody and is directed to the target where it either binds to the cell surface antigen, receptor or the ligand of the targeted disease. Cytotoxicity is mediated by the protein toxins, which maybe protein at times.
The cytotoxic part may comprise of any molecule which has the capability to induce cell death either by interfering with the cell machinery, modifying cell membrane, or by induction of apoptotic pathways. The cytotoxicity thus successfully delivered either to cytoplasm or the ribosomes of the target cell may be lethal to the cell.
During its ignition era, immunotoxins basically comprised of monoclonal antibodies (MAb) or growth factors chemically conjugated to protein toxins by the formation of the disulphide bonds. These molecules contained full length protein toxins are were not that cell specific. With progress in the research and technology, second generation immunotoxins made an entry. They were modulated in a way to remove the toxin mediated cell binding and spare the normal cells from cytotoxicity. The immunotoxins of this generation contained full length Immunoglobulin (IgG) bound to the toxic moiety.
The entry of third generation was marked by coming of recombinant technology which was targeted to remove the immunogenicity by shifting from murine origin immunoglobulins to humanized recombinant IgGs. The molecules of this generation thus formed consisted of fragments of variable domain (Fv) conjugated to IgG. Thus, created immunotoxins had excellent activity, specificity, better penetration and less immunogenicity.
Immunotoxins continue to be actively investigated as viable alternatives to conventional therapies for a variety of diseases. An array of different recombinant, antibody formats are now available for use in immunotoxins. While these design changes have improved the overall in vitro and preclinical in vivo efficacy of immunotoxins, increased potency does not address either of the two major concerns for drugs of this type: immunogenicity and toxicity.
In the past three to four decades, a wide variety of immunotoxins have been tested against a wide variety of malignancies in cell culture, in animal models, and in patients. The most useful of these agents appear to be the relatively small recombinant fusion toxins that contain either growth factor or Fv fragments as ligands. The most sensitive diseases appear to be hematologic malignancies. Future development will need to address combinations of immunotoxins with other anticancer therapies in order to overcome problems of tumor penetration, toxicity, and immunogenicity.
After many years of pre-clinical development, there has been a recent burst in the number of clinical trials using antibodies or antibody fragments to target potent cytotoxic molecules to cancer cells. Several of these trials have shown impressive clinical responses indicating that we are at the beginning of a new and exciting phase of cancer treatment. Additional studies are now required to define the optimal dose, schedule, and combinations for specific malignancies. Also several problems have been identified. One of these is immunogenicity, which may be solved by removing B and T cell epitopes. Another is likely to be drug and toxin resistance. Never the less we expect this new approach is likely to have a major impact in cancer treatment.
“Global Cancer Immunotoxins Market & Clinical Pipeline Insight 2020” Report Highlights:
- Introduction to Immunotoxins
- Cancer Immunotoxins Therapy Analysis
- Advantages of Immunotoxins upon other Anticancerous Drugs
- Applications of Immunotoxins to Multiple Cancer Therapies
- Global Cancer Immunotoxins Market Future Prospects
- Global Cancer Immunotoxins Clinical Pipeline by Company, Indication & Phase
- Global Cancer Immunotoxins Clinical Pipeline: 52 Cancer Immunotoxins
- Majority Cancer Immunotoxins in Preclinical Phase: 21 Drugs
1. INTRODUCTION TO IMMUNOTOXINS
2. IMMUNOTOXINS: THE THREE GENERATIONS & ADVANCEMENTS
3. SOURCES OF TOXINS
3.1 Plant Toxins
3.2 Bacterial Toxins
4. PRODUCTION OF IMMUNOTOXINS
5. TYPES OF IMMUNOTOXINS
5.1 Anthrax Based Toxins
5.2 Diphtheria Toxin (DT) & DT Derivatives
5.3 Pseudomonas Exotoxin (PE) & PE Derivatives
5.4 Ribosome Inactivating Proteins Based Immunotoxins
5.4.1 Ricin
5.4.2 Saporin based Immunotoxins
5.4.3 Recombinant Constructs of RIP I Toxins
5.5 Ribonucleases based Immunotoxins
5.6 Proapoptotic Proteins as Targeted Immunotoxins
6. CANCER IMMUNOTOXINS THERAPY ANALYSIS
6.1 Immunotoxins for Hematologic Malignancies
6.1.1 Denileukin Diftitox (ONTAK, DAB389IL-2)
6.1.2 LMB-2 (anti-Tac[Fv]-PE38)
6.1.3 Moxetumomab Pasudotox
6.1.4 A-dmDT390-bisFv (UCHT1)
6.1.5 DT2219ARL
6.1.6 HuM195-Gelonin
6.2 Immunotoxins for Solid Tumors
6.2.1 SS1P
6.2.2 RG7787
6.2.3 Oportuzumab Monatox
6.2.4 VB6-845
6.2.5 D2C7-(scdsFv)-PE38KDEL
7. ADVANTAGES OF IMMUNOTOXINS UPON OTHER ANTICANCEROUS DRUGS
8. APPLICATIONS OF IMMUNOTOXINS
8.1 Immunotoxins against Solid Tumors
8.1.1 Immunotoxin against Colon Carcinoma
8.1.2 Immunotoxin against Breast Cancer & Sarcoma
8.1.3 Immunotoxin against Glioma & Head & Neck Squamous Cell Carcinoma
8.1.4 Immunotoxin against Prostate & Lung Cancer
8.2 Immunotoxins against Leukemias
8.3 Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected Cell Reservoirs
9. GLOBAL CANCER IMMUNOTOXINS MARKET OUTLOOK
9.1 Current Market Scenario
9.2 Cancer Immunotoxins Clinical Pipeline Overview
10. GLOBAL CANCER IMMUNOTOXINS MARKET DYNAMICS
10.1 Favorable Parameters
10.1.1 Large Segment of Patient Still Devoid of Appropriate Medication
10.1.2 Cancer: A Severe Pathological Condition
10.1.3 Unmet Requirement of Completely Curative Agents
10.1.4 Unwanted Effects of the Existing Drugs
10.2 Commercialization Challenges
10.2.1 Stern Regulatory Guidelines: A Major Hurdle
10.2.2 Never Ending Phase of Research & Development
10.2.3 Conduction of Clinical Trials
10.2.4 Funding Research & Development: A Super Costly Affair
10.2.5 Immunogenicity of Immunotoxins
11. GLOBAL CANCER IMMUNOTOXINS MARKET FUTURE PROSPECTS
12. GLOBAL CANCER IMMUNOTOXINS CLINICAL PIPELINE BY COMPANY, INDICATION & PHASE
12.1 Research
12.2 Preclinical
12.3 Phase-I
12.4 Phase-I/II
12.5 Phase-II
12.6 Phase-II/III
12.7 Phase-III
13. DISCONTINUED & NO DEVELOPMENT IN CANCER IMMUNOTOXINS CLINICAL PIPELINE BY COMPANY, INDICATION & PHASE
13.1 No Development Reported
13.2 Discontinued
13.3 Suspended
14. COMPETITIVE LANDSCAPE
14.1 AbbVie
14.2 AbGenomics
14.3 Agensys
14.4 Ambrx
14.5 Amgen
14.6 AREVA Med
14.7 Bayer HealthCare
14.8 Biotest
14.9 Celldex Therapeutics
14.10 CuraGen Corporation
14.11 Genentech
14.12 Genmab
14.13 Heidelberg Pharma
14.14 ImmunoGen
14.15 Neurocrine Biosciences
14.16 Research Corporation Technologies
14.17 Sanofi
14.18 Seattle Genetics
14.19 Sorrento Therapeutics
14.20 Spirogen
2. IMMUNOTOXINS: THE THREE GENERATIONS & ADVANCEMENTS
3. SOURCES OF TOXINS
3.1 Plant Toxins
3.2 Bacterial Toxins
4. PRODUCTION OF IMMUNOTOXINS
5. TYPES OF IMMUNOTOXINS
5.1 Anthrax Based Toxins
5.2 Diphtheria Toxin (DT) & DT Derivatives
5.3 Pseudomonas Exotoxin (PE) & PE Derivatives
5.4 Ribosome Inactivating Proteins Based Immunotoxins
5.4.1 Ricin
5.4.2 Saporin based Immunotoxins
5.4.3 Recombinant Constructs of RIP I Toxins
5.5 Ribonucleases based Immunotoxins
5.6 Proapoptotic Proteins as Targeted Immunotoxins
6. CANCER IMMUNOTOXINS THERAPY ANALYSIS
6.1 Immunotoxins for Hematologic Malignancies
6.1.1 Denileukin Diftitox (ONTAK, DAB389IL-2)
6.1.2 LMB-2 (anti-Tac[Fv]-PE38)
6.1.3 Moxetumomab Pasudotox
6.1.4 A-dmDT390-bisFv (UCHT1)
6.1.5 DT2219ARL
6.1.6 HuM195-Gelonin
6.2 Immunotoxins for Solid Tumors
6.2.1 SS1P
6.2.2 RG7787
6.2.3 Oportuzumab Monatox
6.2.4 VB6-845
6.2.5 D2C7-(scdsFv)-PE38KDEL
7. ADVANTAGES OF IMMUNOTOXINS UPON OTHER ANTICANCEROUS DRUGS
8. APPLICATIONS OF IMMUNOTOXINS
8.1 Immunotoxins against Solid Tumors
8.1.1 Immunotoxin against Colon Carcinoma
8.1.2 Immunotoxin against Breast Cancer & Sarcoma
8.1.3 Immunotoxin against Glioma & Head & Neck Squamous Cell Carcinoma
8.1.4 Immunotoxin against Prostate & Lung Cancer
8.2 Immunotoxins against Leukemias
8.3 Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected Cell Reservoirs
9. GLOBAL CANCER IMMUNOTOXINS MARKET OUTLOOK
9.1 Current Market Scenario
9.2 Cancer Immunotoxins Clinical Pipeline Overview
10. GLOBAL CANCER IMMUNOTOXINS MARKET DYNAMICS
10.1 Favorable Parameters
10.1.1 Large Segment of Patient Still Devoid of Appropriate Medication
10.1.2 Cancer: A Severe Pathological Condition
10.1.3 Unmet Requirement of Completely Curative Agents
10.1.4 Unwanted Effects of the Existing Drugs
10.2 Commercialization Challenges
10.2.1 Stern Regulatory Guidelines: A Major Hurdle
10.2.2 Never Ending Phase of Research & Development
10.2.3 Conduction of Clinical Trials
10.2.4 Funding Research & Development: A Super Costly Affair
10.2.5 Immunogenicity of Immunotoxins
11. GLOBAL CANCER IMMUNOTOXINS MARKET FUTURE PROSPECTS
12. GLOBAL CANCER IMMUNOTOXINS CLINICAL PIPELINE BY COMPANY, INDICATION & PHASE
12.1 Research
12.2 Preclinical
12.3 Phase-I
12.4 Phase-I/II
12.5 Phase-II
12.6 Phase-II/III
12.7 Phase-III
13. DISCONTINUED & NO DEVELOPMENT IN CANCER IMMUNOTOXINS CLINICAL PIPELINE BY COMPANY, INDICATION & PHASE
13.1 No Development Reported
13.2 Discontinued
13.3 Suspended
14. COMPETITIVE LANDSCAPE
14.1 AbbVie
14.2 AbGenomics
14.3 Agensys
14.4 Ambrx
14.5 Amgen
14.6 AREVA Med
14.7 Bayer HealthCare
14.8 Biotest
14.9 Celldex Therapeutics
14.10 CuraGen Corporation
14.11 Genentech
14.12 Genmab
14.13 Heidelberg Pharma
14.14 ImmunoGen
14.15 Neurocrine Biosciences
14.16 Research Corporation Technologies
14.17 Sanofi
14.18 Seattle Genetics
14.19 Sorrento Therapeutics
14.20 Spirogen
LIST OF FIGURES
Figure 2-1: Immunotoxins & Their Recombinant Forms
Figure 3-1: Sources of Toxins
Figure 4-1: Steps Involved in Production of Immunotoxins
Figure 5-1: Different Types of Immunotoxins
Figure 5-2: Mechanism of Action of Anthrax Based Immunotoxins
Figure 5-3: Composition of the Diphtheria Derived Toxins
Figure 5-4: Steps Involved in Apoptosis by Diphtheria Derived Immunotoxins
Figure 5-5: Domains of PE with Their Specificities
Figure 5-6: Mode of Apoptosis Taken by Pseudomonas Exotoxin (PE) & PE Derivatives
Figure 6-1: Major Targets of Immunotoxins as Anticancer Agents
Figure 6-2: Some of Important Immunotoxins Targeting Hematological Malignancies
Figure 6-3: Some of Important Immunotoxins Targeting Solid Tumors
Figure 8-1: Major Applications of Immunotoxins
Figure 9-1: Cancer Immunotoxins Pipeline by Phase (%), 2016
Figure 9-2: Cancer Immunotoxins Pipeline by Phase (Numbers), 2016
Figure 9-3: Cancer Immunotoxins Pipeline by Phase (%), 2016
Figure 9-4: Cancer Immunotoxins Pipeline by Phase (Numbers), 2016
Figure 10-1: Favorable Parameters for Global Cancer Immunotoxins Market
Figure 10-2: Commercialization Challenges for Global Cancer Immunotoxins Market
Figure 14-1: AbGenomics - Clinical Pipeline
Figure 14-2: Amgen - Clinical Pipeline
Figure 14-3: Biotest – Clinical Pipeline
Figure 14-4: Genmab - Clinical Pipeline
Figure 14-50: Genmab - Clinical Pipeline
Figure 14-6: Neurocrine Biosciences – Clinical Pipeline
Figure 14-7: Sorrento Therapeutics – Clinical Pipeline
Figure 2-1: Immunotoxins & Their Recombinant Forms
Figure 3-1: Sources of Toxins
Figure 4-1: Steps Involved in Production of Immunotoxins
Figure 5-1: Different Types of Immunotoxins
Figure 5-2: Mechanism of Action of Anthrax Based Immunotoxins
Figure 5-3: Composition of the Diphtheria Derived Toxins
Figure 5-4: Steps Involved in Apoptosis by Diphtheria Derived Immunotoxins
Figure 5-5: Domains of PE with Their Specificities
Figure 5-6: Mode of Apoptosis Taken by Pseudomonas Exotoxin (PE) & PE Derivatives
Figure 6-1: Major Targets of Immunotoxins as Anticancer Agents
Figure 6-2: Some of Important Immunotoxins Targeting Hematological Malignancies
Figure 6-3: Some of Important Immunotoxins Targeting Solid Tumors
Figure 8-1: Major Applications of Immunotoxins
Figure 9-1: Cancer Immunotoxins Pipeline by Phase (%), 2016
Figure 9-2: Cancer Immunotoxins Pipeline by Phase (Numbers), 2016
Figure 9-3: Cancer Immunotoxins Pipeline by Phase (%), 2016
Figure 9-4: Cancer Immunotoxins Pipeline by Phase (Numbers), 2016
Figure 10-1: Favorable Parameters for Global Cancer Immunotoxins Market
Figure 10-2: Commercialization Challenges for Global Cancer Immunotoxins Market
Figure 14-1: AbGenomics - Clinical Pipeline
Figure 14-2: Amgen - Clinical Pipeline
Figure 14-3: Biotest – Clinical Pipeline
Figure 14-4: Genmab - Clinical Pipeline
Figure 14-50: Genmab - Clinical Pipeline
Figure 14-6: Neurocrine Biosciences – Clinical Pipeline
Figure 14-7: Sorrento Therapeutics – Clinical Pipeline
LIST OF TABLES
Table 5-1: Immunotoxins in Clinical Development using Diphtheria as a Toxin Moiety
Table 5-2: Clinically evaluated/under evaluation PE-based Immunotoxins against Hematologic Malignancies
Table 5-3: Clinically evaluated/under evaluation PE-based Immunotoxins against Solid Tumors
Table 5-4: Clinical Trials in Patients with Saporin Containing Immunotoxins
Table 6-1: Immunotoxins for Leukemia
COMPANIES MENTIONED
AbbVie, AbGenomics, Agensys, Ambrx, Amgen, AREVA Med, Bayer HealthCare, Biotest, Celldex Therapeutics, CuraGen Corporation, Genentech, Genmab, Heidelberg Pharma, ImmunoGen, Neurocrine Biosciences, Research Corporation Technologies, Sanofi, Seattle Genetics, Sorrento Therapeutics, Spirogen
Table 5-1: Immunotoxins in Clinical Development using Diphtheria as a Toxin Moiety
Table 5-2: Clinically evaluated/under evaluation PE-based Immunotoxins against Hematologic Malignancies
Table 5-3: Clinically evaluated/under evaluation PE-based Immunotoxins against Solid Tumors
Table 5-4: Clinical Trials in Patients with Saporin Containing Immunotoxins
Table 6-1: Immunotoxins for Leukemia
COMPANIES MENTIONED
AbbVie, AbGenomics, Agensys, Ambrx, Amgen, AREVA Med, Bayer HealthCare, Biotest, Celldex Therapeutics, CuraGen Corporation, Genentech, Genmab, Heidelberg Pharma, ImmunoGen, Neurocrine Biosciences, Research Corporation Technologies, Sanofi, Seattle Genetics, Sorrento Therapeutics, Spirogen
