DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Chan Hyuk | ko |
dc.contributor.author | Axup, Jun Y. | ko |
dc.contributor.author | Lawson, Brian R. | ko |
dc.contributor.author | Yun, Hwayoung | ko |
dc.contributor.author | Tardif, Virginie | ko |
dc.contributor.author | Choi, Sei Hyun | ko |
dc.contributor.author | Zhou, Quan | ko |
dc.contributor.author | Dubrovska, Anna | ko |
dc.contributor.author | Biroc, Sandra L. | ko |
dc.contributor.author | Marsden, Robin | ko |
dc.contributor.author | Pinstaff, Jason | ko |
dc.contributor.author | Smider, Vaughn V. | ko |
dc.contributor.author | Schultz, Peter G. | ko |
dc.date.accessioned | 2016-07-04T06:02:46Z | - |
dc.date.available | 2016-07-04T06:02:46Z | - |
dc.date.created | 2016-05-13 | - |
dc.date.created | 2016-05-13 | - |
dc.date.created | 2016-05-13 | - |
dc.date.issued | 2013-10 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.110, no.44, pp.17796 - 17801 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/209134 | - |
dc.description.abstract | Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant alpha CD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 similar to 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | UNNATURAL AMINO-ACIDS | - |
dc.subject | T-CELL-ACTIVATION | - |
dc.subject | MEMBRANE ANTIGEN | - |
dc.subject | ESCHERICHIA-COLI | - |
dc.subject | B-LINEAGE | - |
dc.subject | IN-VIVO | - |
dc.subject | THERAPY | - |
dc.subject | IMMUNOTHERAPY | - |
dc.subject | BINDING | - |
dc.subject | BLINATUMOMAB | - |
dc.title | Bispecific small molecule-antibody conjugate targeting prostate cancer | - |
dc.type | Article | - |
dc.identifier.wosid | 000326243100048 | - |
dc.identifier.scopusid | 2-s2.0-84887046901 | - |
dc.type.rims | ART | - |
dc.citation.volume | 110 | - |
dc.citation.issue | 44 | - |
dc.citation.beginningpage | 17796 | - |
dc.citation.endingpage | 17801 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1316026110 | - |
dc.contributor.localauthor | Kim, Chan Hyuk | - |
dc.contributor.nonIdAuthor | Axup, Jun Y. | - |
dc.contributor.nonIdAuthor | Lawson, Brian R. | - |
dc.contributor.nonIdAuthor | Yun, Hwayoung | - |
dc.contributor.nonIdAuthor | Tardif, Virginie | - |
dc.contributor.nonIdAuthor | Choi, Sei Hyun | - |
dc.contributor.nonIdAuthor | Zhou, Quan | - |
dc.contributor.nonIdAuthor | Dubrovska, Anna | - |
dc.contributor.nonIdAuthor | Biroc, Sandra L. | - |
dc.contributor.nonIdAuthor | Marsden, Robin | - |
dc.contributor.nonIdAuthor | Pinstaff, Jason | - |
dc.contributor.nonIdAuthor | Smider, Vaughn V. | - |
dc.contributor.nonIdAuthor | Schultz, Peter G. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | antibody engineering | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.subject.keywordPlus | UNNATURAL AMINO-ACIDS | - |
dc.subject.keywordPlus | T-CELL-ACTIVATION | - |
dc.subject.keywordPlus | MEMBRANE ANTIGEN | - |
dc.subject.keywordPlus | ESCHERICHIA-COLI | - |
dc.subject.keywordPlus | B-LINEAGE | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | BLINATUMOMAB | - |
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