immunotoxin

免疫毒素

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/03 03:58:07」(JST)

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For other uses, see Immunosuppressant.

An immunotoxin is a human-made protein that consists of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell.^[1] They are used for the treatment of some kinds of cancer and a few viral infections.

Design

These chimeric proteins are usually made of a modified antibody or antibody fragment, attached to a fragment of a toxin. The targeting portion is composed of the Fv portion of an antibody that targets a specific cell type.^[2] The toxin is usually a cytotoxic protein derived from a bacterial or plant protein, from which the natural binding domain has been removed so that the Fv directs the toxin to the antigen on the target cell.^[1]

Sometimes recombinant fusion proteins containing a toxin and a growth factor are also referred to as recombinant immunotoxins, although they do not contain an antibody fragment. A more specific name for this latter kind of protein is recombinant fusion toxin.

Production

They were originally produced by attaching the antibody to the toxin using a chemical linker.^{[citation needed]} They are now made using recombinant DNA techniques, are produced in bacteria like E. coli or yeast like P. pastoris and are called recombinant immunotoxins.

Function

The antibody (or other targeting moiety) binds to an antigen on the target cell and the toxin then enters and kills the cell.

Clinical application

The best clinical success has been achieved in treating patients with refractory hairy cell leukemia.^{[citation needed]} These patients were treated with the recombinant immunotoxin, BL22, which targets the CD22 cell surface receptor, which is highly expressed on these leukemic cells. In two uncontrolled clinical studies, about half of participants achieved a complete response after BL22 treatment.^[3] This therapeutic has been superseded by HA22, a slightly modified version.

A recent Phase I study of Resimmune found a 100% response rate in a subgroup of six patients with cutaneous T cell lymphoma.^[4] This subgroup was Stage IB-IIB with mSWAT scores of less than 50. The complete response rate was 67% (two of which are over 36 and 42 months duration and could represent cures).

References

^ ^a ^b Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ (2007). "Immunotoxin treatment of cancer". Annu. Rev. Med. 58: 221–37. doi:10.1146/annurev.med.58.070605.115320. PMID 17059365.
^ Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ (July 2006). "Immunotoxin therapy of cancer". Nat. Rev. Cancer 6 (7): 559–65. doi:10.1038/nrc1891. PMID 16794638.
^ Kreitman RJ, Wilson WH, Bergeron K, et al (July 2001). "Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia". N. Engl. J. Med. 345 (4): 241–7. doi:10.1056/NEJM200107263450402. PMID 11474661. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=11474661&promo=ONFLNS19.
^ [1] Angimmune: Clinical Trials: Identification of a Cutaneous T-Cell Lymphoma (CTCL) Subgroup Experiencing a High Treatment Response Rate: Paragraph 1

External links

immunotoxins at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 有毛細胞白血病の治療 treatment of hairy cell leukemia
2. 初期化学療法後の再発古典型ホジキンリンパ腫の治療 treatment of relapse of classical hodgkin lymphoma after initial chemotherapy
3. 移植片対宿主病の予防および治療に使用される免疫抑制剤の概要 overview of immunosuppressive agents used for prevention and treatment of graft versus host disease
4. 急性移植片対宿主病の治療：臨床試験 treatment of acute graft versus host disease clinical trials
5. 再発または治療抵抗性古典的ホジキンリンパ腫に対するセカンドラインおよび
サードライン化学療法レジメン second and third line chemotherapy regimens for relapsing or resistant classical hodgkin lymphoma

English Journal

In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA' in a human acute myeloid leukemia xenograft tumor model.

Tur MK, Huhn M, Jost E, Thepen T, Brummendorf TH, Barth S.SourceDepartment of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, University Hospital RWTH Aachen, Aachen, Germany. tur@hia.rwth-aachen.de
International journal of cancer. Journal international du cancer.Int J Cancer.2011 Sep 1;129(5):1277-82. doi: 10.1002/ijc.25766. Epub 2011 Feb 26.
Target-specific acute myeloid leukemia (AML) immunotherapy requires selective cell-surface antigens on AML blast cells. CD64 is a promising candidate antigen because it is abundantly expressed on monocytoid differentiated AML subtypes. In previous studies, a chemically linked full-length anti-CD64 i
PMID 21077160

Colocalization of gadolinium-diethylene triamine pentaacetic Acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans.

Sampson JH, Brady M, Raghavan R, Mehta AI, Friedman AH, Reardon DA, Petry NA, Barboriak DP, Wong TZ, Zalutsky MR, Lally-Goss D, Bigner DD.Source*Division of Neurosurgery, Department of Surgery; ‡Department of Pathology, Duke University Medical Center, Durham, North Carolina; §Therataxis, LLC, Baltimore, Maryland; Departments of ?Pediatrics and ¶Radiology, Duke University Medical Center, Durham, North Carolina.
Neurosurgery.Neurosurgery.2011 Sep;69(3):668-76.
BACKGROUND: : Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents th
PMID 21430586

Japanese Journal

Proposal of Minimal Invasive Shape Memory Alloy Double-Transducer Unit for Blood Analysis or Drug Delivery

YAMAMOTO Hidetake
Journal of Biomechanical Science and Engineering 6(3), 203-212, 2011
… The author has focused on lymphocytes for immunotoxin and erythrocytes for the glucose level in blood. …
NAID 130000771947