Immunotoxins - Biotech, Pharma and Life Science Channel

16:37 EDT 27th October 2016 | 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 [15 Associated Clinical Trials listed on BioPortfolio]

A Phase I Study of the Reduced Immunogenicity Mesothelin-Targeted Immunotoxin LMB-100 in Patients With Malignant Mesothelioma

Background: - Although mesothelioma patients with a limited tumor burden may benefit from surgical resection, most patients have advanced disease at diagnosis and are not candidat...

Collection of Human Samples to Study Hairy Cell and Other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment

Background: - Researchers who are studying hairy cell leukemia, and how the disease compares with other disorders, are interested in obtaining additional samples from leukemia patients an...

Multi-Tracer PET in Early Phase Trials

The treatment of cancer is increasingly aimed at molecular targets derived from studies of the oncogenes and tumor suppressors known to be involved in the development of human cancers. The...

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...

PubMed Articles [10 Associated PubMed Articles listed on BioPortfolio]

Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins.

The intersection of small molecular weight drugs and antibody-based therapeutics is rarely studied in large scale. Both types of agents are currently part of the cancer armamentarium. However, very li...

Saponins from Saponaria officinalis L. Augment the Efficacy of a Rituximab-Immunotoxin.

Triterpenoidal saponins are synthesized in the roots of Saponaria officinalis L. The same plant is also a source for the toxin Saporin, which is a ribosome-inactivating protein. Triterpenoidal saponin...

Improved Synthesis and In Vitro Evaluation of an Aptamer Ribosomal Toxin Conjugate.

Delivery of toxins, such as the ricin A chain, Pseudomonas exotoxin, and gelonin, using antibodies has had some success in inducing specific toxicity in cancer treatments. However, these antibody-toxi...

Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin Targeting Recombinant Immunotoxins.

Mesothelin (MSLN) is a differentiation antigen that is highly expressed in many epithelial cancers. MSLN is an important therapeutic target due to its high expression in cancers and limited expression...

Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts.

Rejection of donor organs depends on the trafficking of donor passenger leukocytes to the secondary lymphoid organs of the recipient to elicit an immune response via the direct antigen presentation pa...

Anti-Human Endoglin (hCD105) Immunotoxin-Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1.

Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endo...

Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotox...

Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers.

Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling ha...

Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers.

The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the...

Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A.

Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical tri...


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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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