Source:http://linkedlifedata.com/resource/pubmed/id/17784727
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2007-10-2
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| pubmed:abstractText |
Targeting of malignancies with folate-linked therapeutics has proven to be a promising endeavor due to the preferential expression of folate receptors (FR) on human tumors. We have shown that folic acid (pteroyl-glutamate) can be used to deliver an antigenic hapten, fluorescein, to the surface of tumor cells to promote their opsonization within a fluorescein-immunized host. Here, we investigate structure-activity relationships among members of another class of folate-hapten conjugates ( EC57, EC63, EC0293, and EC0294), namely, those containing the dinitrophenyl (DNP) group as the antigenic hapten. We report that despite exhibiting similar affinities for the FR, the antitumor activity and allergic potential of these DNP conjugates varied depending on their linker chemistries and abilities to bind anti-DNP IgG/IgE antibodies. Unlike EC57 and EC63, both EC0293 and EC0294 (i) share the identical DNP bridging chemistry to that found in keyhole limpet hemocyanin (KLH)-DNP (i.e., the immunogen), (ii) efficiently recognize DNP-specific IgG, and (iii) mediate more pronounced antitumor responses. However, EC0293 and EC0294 were also found to recognize DNP-specific IgE, and they displayed a greater risk of allergy when evaluated in a passive cutaneous anaphylaxis assay. Nonetheless, upon co-stimulation with the appropriate cytokines (IL-2/IFN-alpha), the folate-targeted "haptenization" process allowed for tumor rejection and protective antitumor immunity without causing any visible allergy in immunized mice. Our data further support the concept that folate-hapten-targeted immunotherapy may offer an effective therapeutic option for treatment of FR-positive cancers, but such treatment should proceed with caution given the risk of a potential allergic reaction.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Allergens,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Haptens,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrogen
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| pubmed:status |
MEDLINE
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| pubmed:issn |
1543-8384
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
4
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
695-706
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| pubmed:meshHeading |
pubmed-meshheading:17784727-Allergens,
pubmed-meshheading:17784727-Animals,
pubmed-meshheading:17784727-Antibodies,
pubmed-meshheading:17784727-Antineoplastic Agents,
pubmed-meshheading:17784727-Cell Line, Tumor,
pubmed-meshheading:17784727-Cross-Linking Reagents,
pubmed-meshheading:17784727-Drug Delivery Systems,
pubmed-meshheading:17784727-Female,
pubmed-meshheading:17784727-Folic Acid,
pubmed-meshheading:17784727-Haptens,
pubmed-meshheading:17784727-Immunotherapy,
pubmed-meshheading:17784727-Interferon-alpha,
pubmed-meshheading:17784727-Interleukin-2,
pubmed-meshheading:17784727-Mice,
pubmed-meshheading:17784727-Mice, Inbred BALB C,
pubmed-meshheading:17784727-Molecular Structure,
pubmed-meshheading:17784727-Nitrogen,
pubmed-meshheading:17784727-Rats,
pubmed-meshheading:17784727-Substrate Specificity,
pubmed-meshheading:17784727-Survival Rate,
pubmed-meshheading:17784727-Xenograft Model Antitumor Assays
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| pubmed:articleTitle |
Folate-targeted dinitrophenyl hapten immunotherapy: effect of linker chemistry on antitumor activity and allergic potential.
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| pubmed:affiliation |
Endocyte Inc., West Lafayette, IN 47906, USA.
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| pubmed:publicationType |
Journal Article
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