Transferrin Receptor Ligand-Targeted Toxin Conjugate (Tf-CRM107) for Therapy of Malignant Gliomas
Identifieur interne : 002051 ( Main/Exploration ); précédent : 002050; suivant : 002052Transferrin Receptor Ligand-Targeted Toxin Conjugate (Tf-CRM107) for Therapy of Malignant Gliomas
Auteurs : Michael Weaver [États-Unis] ; Douglas W. Laske [États-Unis]Source :
- Journal of Neuro-Oncology [ 0167-594X ] ; 2003-10-01.
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Abstract
Abstract: The authors review the preclinical and clinical results of the ligand-targeted toxin conjugate Transferrin-CRM107 (Tf-CRM107), for the treatment of malignant gliomas. Tf-CRM107 is a conjugate protein of diphtheria toxin with a point mutation (CRM107) linked by a thioester bond to human transferrin (Tf). This conjugate exhibits potent cytotoxicity in vitro against mammalian cells expressing the transferrin receptor with activity at picomolar concentrations. Phase I clinical trial results demonstrated that Tf-CRM107, delivered via a high-flow convection method utilizing stereotactically placed catheters, produced tumor response in patients with malignant brain tumors refractory to conventional therapy without severe neurologic or systemic toxicity. The results of a Phase II study are also summarized. Tf-CRM107 treatment results in complete and partial tumor response without severe toxicity in 35% of the evaluable patients. These data warrant a Phase III study as well as continued research in the field of targeted toxin therapy. Future directions of research include optimizing Tf-CRM107 delivery to targeted brain regions, and improving the treatment efficacy by combining with other toxin conjugates targeted to different receptors.
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DOI: 10.1023/A:1026246500788
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Laske</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurosurgery, Temple University School of Medicine, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neuro-Oncology</title><title level="j" type="abbrev">J Neurooncol</title><idno type="ISSN">0167-594X</idno><idno type="eISSN">1573-7373</idno><imprint><publisher>Kluwer Academic Publishers</publisher><pubPlace>Boston</pubPlace><date type="published" when="2003-10-01">2003-10-01</date><biblScope unit="volume">65</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="3">3</biblScope><biblScope unit="page" to="14">14</biblScope></imprint><idno type="ISSN">0167-594X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0167-594X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>convection enhanced delivery</term><term>diphtheria toxin</term><term>glioblastoma multiforme (GBM)</term><term>malignant brain tumor</term><term>targeted toxin</term><term>transferrin</term><term>transferrin receptor</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The authors review the preclinical and clinical results of the ligand-targeted toxin conjugate Transferrin-CRM107 (Tf-CRM107), for the treatment of malignant gliomas. Tf-CRM107 is a conjugate protein of diphtheria toxin with a point mutation (CRM107) linked by a thioester bond to human transferrin (Tf). This conjugate exhibits potent cytotoxicity in vitro against mammalian cells expressing the transferrin receptor with activity at picomolar concentrations. Phase I clinical trial results demonstrated that Tf-CRM107, delivered via a high-flow convection method utilizing stereotactically placed catheters, produced tumor response in patients with malignant brain tumors refractory to conventional therapy without severe neurologic or systemic toxicity. The results of a Phase II study are also summarized. Tf-CRM107 treatment results in complete and partial tumor response without severe toxicity in 35% of the evaluable patients. These data warrant a Phase III study as well as continued research in the field of targeted toxin therapy. Future directions of research include optimizing Tf-CRM107 delivery to targeted brain regions, and improving the treatment efficacy by combining with other toxin conjugates targeted to different receptors.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Weaver, Michael" sort="Weaver, Michael" uniqKey="Weaver M" first="Michael" last="Weaver">Michael Weaver</name></region><name sortKey="Laske, Douglas W" sort="Laske, Douglas W" uniqKey="Laske D" first="Douglas W." last="Laske">Douglas W. Laske</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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