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dc.contributor.authorGalili, Uri
dc.contributor.authorWigglesworth, Kim
dc.contributor.authorAbdel-Motal, Ussama M.
dc.date2022-08-11T08:09:32.000
dc.date.accessioned2022-08-23T16:34:51Z
dc.date.available2022-08-23T16:34:51Z
dc.date.issued2007-03-21
dc.date.submitted2009-03-16
dc.identifier.citation<p>J Immunol. 2007 Apr 1;178(7):4676-87.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.178.7.4676
dc.identifier.pmid17372027
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38428
dc.description.abstractThis study describes a novel cancer immunotherapy treatment that exploits the natural anti-Gal Ab to destroy tumor lesions and convert them into an endogenous vaccine targeted to APC via FcgammaR. Anti-Gal constitutes 1% of immunoglobulins in humans and interacts specifically with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R). The binding of anti-Gal to alpha-gal epitopes on pig cells mediates xenograft rejection. The proposed method uses glycolipid micelles with multiple alpha-gal epitopes (alpha-gal glycolipids). These glycolipids are extracted from rabbit red cell membranes and are comprised of ceramides with carbohydrate chains containing 5-25 carbohydrates, all capped with alpha-gal epitopes. Efficacy of this treatment was demonstrated in alpha1,3-galactosyltransferase knockout mice producing anti-Gal and bearing B16 melanoma or B16/OVA producing OVA as a surrogate tumor Ag. These mice are unique among nonprimate mammals in that, similar to humans, they lack alpha-gal epitopes and can produce the anti-Gal Ab. Intratumoral injection of alpha-gal glycolipids results in local inflammation mediated by anti-Gal binding to the multiple alpha-gal epitopes and activation of complement. These glycolipids spontaneously insert into tumor cell membranes. The binding of anti-Gal to alpha-gal expressing tumor cells induces the destruction of treated lesions as in anti-Gal-mediated xenograft rejection. Anti-Gal further opsonizes tumor cells within the lesion and, thus, targets them for effective uptake by APC that transport the tumor Ags to draining lymph nodes. APC further cross-present immunogenic tumor Ag peptides and elicit a systemic anti-tumor immune response. Similar intratumoral injection of alpha-gal glycolipids in humans is likely to induce the destruction of treated lesions and elicit a protective immune response against micrometastases.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17372027&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.178.7.4676
dc.subjectAnimals
dc.subjectAntigen Presentation
dc.subjectAntigen-Presenting Cells
dc.subjectAntigens, Neoplasm
dc.subjectCancer Vaccines
dc.subjectCarbohydrate Sequence
dc.subjectDendritic Cells
dc.subjectErythrocyte Membrane
dc.subjectGalactosyltransferases
dc.subjectGlycolipids
dc.subjectImmunotherapy
dc.subjectInjections
dc.subjectLymph Nodes
dc.subjectLymphocytes, Tumor-Infiltrating
dc.subjectMelanoma, Experimental
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMolecular Sequence Data
dc.subjectOvalbumin
dc.subjectRabbits
dc.subjectSkin Neoplasms
dc.subjectTransplantation, Heterologous
dc.subjectTrisaccharides
dc.subjectXenograft Model Antitumor Assays
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleIntratumoral injection of alpha-gal glycolipids induces xenograft-like destruction and conversion of lesions into endogenous vaccines
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume178
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1295
dc.identifier.contextkey782965
html.description.abstract<p>This study describes a novel cancer immunotherapy treatment that exploits the natural anti-Gal Ab to destroy tumor lesions and convert them into an endogenous vaccine targeted to APC via FcgammaR. Anti-Gal constitutes 1% of immunoglobulins in humans and interacts specifically with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R). The binding of anti-Gal to alpha-gal epitopes on pig cells mediates xenograft rejection. The proposed method uses glycolipid micelles with multiple alpha-gal epitopes (alpha-gal glycolipids). These glycolipids are extracted from rabbit red cell membranes and are comprised of ceramides with carbohydrate chains containing 5-25 carbohydrates, all capped with alpha-gal epitopes. Efficacy of this treatment was demonstrated in alpha1,3-galactosyltransferase knockout mice producing anti-Gal and bearing B16 melanoma or B16/OVA producing OVA as a surrogate tumor Ag. These mice are unique among nonprimate mammals in that, similar to humans, they lack alpha-gal epitopes and can produce the anti-Gal Ab. Intratumoral injection of alpha-gal glycolipids results in local inflammation mediated by anti-Gal binding to the multiple alpha-gal epitopes and activation of complement. These glycolipids spontaneously insert into tumor cell membranes. The binding of anti-Gal to alpha-gal expressing tumor cells induces the destruction of treated lesions as in anti-Gal-mediated xenograft rejection. Anti-Gal further opsonizes tumor cells within the lesion and, thus, targets them for effective uptake by APC that transport the tumor Ags to draining lymph nodes. APC further cross-present immunogenic tumor Ag peptides and elicit a systemic anti-tumor immune response. Similar intratumoral injection of alpha-gal glycolipids in humans is likely to induce the destruction of treated lesions and elicit a protective immune response against micrometastases.</p>
dc.identifier.submissionpathoapubs/1295
dc.contributor.departmentDepartment of Medicine
dc.source.pages4676-87


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