Immunotoxins - Biotech, Pharma and Life Science Channel

07:46 EDT 2nd September 2014 | BioPortfolio

Immunotoxins are proteins that contain a toxin along with an antibody or growth factor that binds specifically to target cells. Nearly all protein toxins work by enzymatically inhibiting protein synthesis. For the immunotoxin to work, it must bind to and be internalized by the target cells, and the enzymatic fragment of the toxin must translocate to the cytosol. Once in the cytosol, 1 molecule is capable of killing a cell, making immunotoxins some of the most potent killing agents

Immunotoxin therapy is a promising molecular cancer treatment strategy. Its main advantage is seletive cytotoxicity towards tumor cells and minimal toxicity in normal tissues. At present ten immunotoxins are in phase II or higher stages of clinical development and eight projects in early clinical evaluation. At present, only 1 agent, which contains human interleukin-2 and truncated diphtheria toxin, is approved for use in cutaneous T-cell lymphoma. Another, containing an anti-CD22 Fv and truncated Pseudomonas exotoxin, has induced complete remissions in a high proportion of cases of hairy-cell leukemia. Refinement of existing immunotoxins and development of new immunotoxins are underway to improve the treatment of cancer.

Hematologic malignancies are optimal for treating with immunotoxins, since malignant cells are often intravascular and accessible to intravenously administered drug, and since patients often lack sufficient immunity to make antibodies against the toxin. Targeting solid tumors with immunotoxins is much more difficult than targeting hematologic tumors. The challenges associated with the development of many immunotoxins for cancer therapy include immunogenicity, unwanted toxicity, difficulty in production, limited half-life, and resistance.

In the past 3 to 4 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.

Source; Kreitman RJ. Immunotoxins for Targeted Cancer Therapy. AAPS Journal. 2006; 8(3): E532-E551.

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Clinical Trials [13 Associated Clinical Trials listed on BioPortfolio]

Immunotoxin in Treating Patients With Leukemia or Lymphoma

RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effecti...

Denileukin Diftitox in Treating Patients With Non-Hodgkin's Lymphoma

RATIONALE: Immunotoxins such as denileukin diftitox can locate cancer cells and kill them without harming normal cells. This may be an effective treatment for non-Hodgkin's lymphoma. PURP...

Immunotoxin Therapy in Treating Patients With Malignant Glioma

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for malignant glioma. PURPOSE: Phase I/II trial to study the ...

Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be an effective treatment for glioblastoma multiforme and anaplastic astr...

Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating advanced solid tumors. PURPOSE: This phase I tr...

Safety and Efficacy Study to Treat Recurrent Grade 4 Malignant Brain Tumors

Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating malignant glioma.

Anti-CD19 and Anti-CD22 Immunotoxins in Treating Patients With Refractory or Relapsed B-Cell Acute Lymphoblastic Leukemia

RATIONALE: Immunotoxins, such as anti-CD19 and anti-CD22, can find cancer cells that express CD19 and CD22 and kill them without harming normal cells. This may be an effective treatment fo...

Immunotoxin Therapy, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer

RATIONALE: Immunotoxins can find certain tumor cells and kill them without harming normal cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to s...

Study of MOC31-PE in Antigen Positive Carcinomas

Immunotoxins (ITs), monoclonal antibodies conjugated to plant or bacterial toxins, have been extensively investigated for their possible use as anti-tumor agents although not in carcinoma ...

RFT5-dgA Immunotoxin in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

RATIONALE: Immunotoxins, such as RFT5-dgA immunotoxin (also called anti-CD25 immunotoxin IMTOX25), can find certain cancer cells and kill them without harming normal cells. PURPOSE: This ...

PubMed Articles [8 Associated PubMed Articles listed on BioPortfolio]

Recombinant immunotoxin for cancer treatment with low immunogenicity by identification and silencing of human T-cell epitopes.

Nonhuman proteins have valuable therapeutic properties, but their efficacy is limited by neutralizing antibodies. Recombinant immunotoxins (RITs) are potent anticancer agents that have produced many c...

Immunotoxins for leukemia.

Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lympho...

Advances in the treatment of hematologic malignancies using immunoconjugates.

Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increa...

CD21(-/low) Marginal Zone B Cells Highly Express Fc Receptor-like 5 Protein and Are Killed by Anti-Fc Receptor-like 5 Immunotoxins in Hepatitis C Virus-Associated Mixed Cryoglobulinemia Vasculitis.

Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non-Hodgkin's lymphoma. The expansion of clonal and autorea...

Effects of a second-generation human anti-ErbB2 ImmunoRNase on trastuzumab-resistant tumors and cardiac cells.

The inhibition of ErbB2 by the use of human antibodies can be a valuable strategy for the treatment of breast and gastric cancer. Trastuzumab, a humanized anti-ErbB2 antibody in clinical use, is effec...

A Reevaluation of CD22 Expression in Human Lung Cancer.

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer ce...

Cytotoxic Effect of Immunotoxin Containing The Truncated Form of Pseudomonas Exotoxin A and Anti-VEGFR2 on HUVEC and MCF-7 Cell Lines.

Immunotoxins (ITs) have been developed for the treatment of cancer, and comprise of antibodies linked to toxins. Also vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis, ...

TWEAK/Fn14 Axis-Targeted Therapeutics: Moving Basic Science Discoveries to the Clinic.

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Medical and Biotech [MESH] Definitions

Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.

Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).

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