Novel immunotoxin: A fusion protein consisting of gelonin and an acetylcholine receptor fragment as a potential immunotherapeutic agent for the treatment of Myasthenia gravis

Hossann, Martin; Li, Zhuoyu; Shi, Yawei; Kreilinger, Ulrike; Büttner, Jörn; Vogel, Pia D.; Yuan, Jingming; Wise, John G.; Trommer, Wolfgang E.

doi:10.1016/j.pep.2005.08.029

Cited by 19 publications

(20 citation statements)

References 38 publications

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“…Chemical and recombinant conjugates of the acetylcholine receptor and gelonin have been employed successfully in studies aimed at the treatment of Experimental Autoimmune Myasthenia Gravis (EAMG) in rats (Hossann et al, 2006;Guo et al, 2005). This study constitutes the first report of the biological activities of full length and truncated gelonins in order to allow identification of the most potent form of gelonin for use as an immunotoxin.…”

Section: Discussionmentioning

confidence: 99%

“…In an attempt of produce antigen-specific suppression of the immune system, conjugates composed of the acetylcholine receptor (AChR) from the electroplax tissue of electric fish such as Torpedo californica and the plant toxin gelonin have been successfully employed in the treatment of rats with Experimental Autoimmune Myasthenia Gravis (EAMG). In addition, a fusion protein composed of 177 N-terminal amino acids of the AchR ␣-subunit C-terminally linked to 247 amino acids of mature gelonin has been reported (Hossann et al, 2006). In this study, we aimed to find the ideal gelonin fragments to conjugate with the acetylcholine receptor for potential medical applications.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we aimed to find the ideal gelonin fragments to conjugate with the acetylcholine receptor for potential medical applications. Three truncated gelonins and intact gelonin (Li et al, 2002;Hossann et al, 2006) were used for in vivo and in vitro experiments. Our findings indicate that the full length gelonin possesses the highest toxicity, whereas there is a distinct reduction of biological function when truncated gelonin is used instead of intact gelonin.…”

Section: Introductionmentioning

confidence: 99%

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Truncations of gelonin lead to a reduction in its cytotoxicity

et al. 2007

Toxicology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Truncations of gelonin lead to a reduction in its cytotoxicity

et al. 2007

Toxicology

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“…Muscle-specific immunotoxins are potential immunotherapeutic agents for the treatment of focal muscle spasm [191], myasthenia gravis [192] and strabismus, by destroying oculomotor muscles [185,[193][194][195]. Other possible uses of immunotoxins in ophthalmology have been explored, for the treatment of posterior capsule opacification, for which some clinical trials have been performed [184,196], and to prevent corneal cell proliferation [197].…”

Section: Removal Of Cells From Cultures [175]mentioning

confidence: 99%

Ribosome-inactivating proteins: progress and problems

Stirpe

Battelli

2006

Cell. Mol. Life Sci.

321

225

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Ribosome-inactivating proteins (RIPs), mostly from plants, are enzymes which depurinate rRNA, thus inhibiting protein synthesis. They also depurinate other polynucleotide substrates. The biological activity of RIPs is not completely clarified, and sometimes independent of the inhibition of protein synthesis. There are differences in the cytotoxicity of RIPs and, consequently, in their toxicity to animals. Some RIPs are potent toxins, the best known being ricin, a potential biological weapon. New toxins have recently been identified. RIPs cause apoptotic and necrotic lesions, and induce production of cytokines causing inflammation. RIPs are potentially useful in agriculture and medicine because (i) they have antiviral activity and (ii) they are used for the preparation of conjugates with antibodies ('immunotoxins') or other carriers, rendering them specifically toxic to the cell target of the carrier, which may be helpful in therapy. The distribution, mechanism of action and role in nature of RIPs are not completely understood, and we can expect several future developments in their practical application.

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“…The autoantigen nicotinic acetylcholine receptor (AChR) of the neuromuscular junction with gelonin was used in the experimental autoimmune M. gravis (EAMG) [39]. Various IT constructs targeting CD5 have been used for diabetes, Graft versus Host Disease (GvHD), RA, Systemic Lupus Erythematosus (SLE) have been studied.…”

Section: Immunotoxins In Autoimmune Disordersmentioning

confidence: 99%