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Immunotoxins - Biotech, Pharma and Life Science Channel

10:49 EDT 23rd July 2017 | 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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News Articles [3 Associated News Articles listed on BioPortfolio]

Molecular Templates Inc Pharmaceuticals Healthcare Deals and Alliances Profile [Updated: 10052017] Prices from USD $250

SummaryMolecular Templates Inc MTI is a biotechnology company that discovers therapies. The company develops, and commercializes immunotoxins for the treatment of cancers and other serious diseases. I...

Missing Pieces of the 'Health Care' Debate

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Molecular Templates Inc Pharmaceuticals Healthcare Deals and Alliances Profile [Updated: 17022017] Prices from USD $250

SummaryMolecular Templates Inc MTI is a biotechnology company that discovers therapies. The company develops, and commercializes immunotoxins for the treatment of cancers and other serious diseases. I...

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Clinical Trials [16 Associated Clinical Trials listed on BioPortfolio]

Inotuzumab Ozogamicin in Treating Younger Patients With Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia

This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with CD22 positive B acute lymphoblastic leukemia that has come back or does not respond to tr...

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.

PubMed Articles [7 Associated PubMed Articles listed on BioPortfolio]

Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma.

We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) usin...

Essential role for Bim in mediating the apoptotic and antitumor activities of immunotoxins.

Protein synthesis is crucial for regulating cell homeostasis and, when unrestricted, it can lead to tumorigenesis. Immunotoxins derived from Pseudomonas exotoxin are antibody-toxin fusion proteins tha...

Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19(+) tumors.

CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of th...

Immunotoxins in cancer therapy: Review and update.

Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, incl...

Fungal Ribotoxins: A Review of Potential Biotechnological Applications.

Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these to...

Humanization of rabbit monoclonal antibodies via grafting combined Kabat/IMGT/Paratome complementarity-determining regions: rationale and examples.

Rabbit monoclonal antibodies (RabMAbs) can recognize diverse epitopes, including those poorly immunogenic in mice and humans. However, there have been only a few reports on RabMAb humanization, an imp...

The Identifications and Clinical Implications of Cancer Stem Cells in Colorectal Cancer.

Cancer stem cells (CSCs) are cancer cells that are responsible for initiation, progression, metastasis, and recurrence in cancer. The aim of this review was to analyze the markers for identifying of C...

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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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