Practical Theoretic Guidance for the Design of Tumor-Targeting Agents
Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic cleara...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101376 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7570-2080 |
| _version_ | 1811082804735246336 |
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| author | Thurber, Greg M. Schmidt, Michael M. Rhoden, John J. Wittrup, Karl Dane |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Thurber, Greg M. Schmidt, Michael M. Rhoden, John J. Wittrup, Karl Dane |
| author_sort | Thurber, Greg M. |
| collection | MIT |
| description | Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles. |
| first_indexed | 2024-09-23T12:09:16Z |
| format | Article |
| id | mit-1721.1/101376 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:09:16Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1013762022-10-01T08:33:40Z Practical Theoretic Guidance for the Design of Tumor-Targeting Agents Thurber, Greg M. Schmidt, Michael M. Rhoden, John J. Wittrup, Karl Dane Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Wittrup, Karl Dane Thurber, Greg M. Schmidt, Michael M. Rhoden, John J. Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles. 2016-02-29T17:12:17Z 2016-02-29T17:12:17Z 2012 Article http://purl.org/eprint/type/JournalArticle 9780123969620 00766879 http://hdl.handle.net/1721.1/101376 Wittrup, K. Dane, Greg M. Thurber, Michael M. Schmidt, and John J. Rhoden. “Practical Theoretic Guidance for the Design of Tumor-Targeting Agents.” Protein Engineering for Therapeutics, Part B (2012): 255–268. https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7570-2080 en_US http://dx.doi.org/10.1016/b978-0-12-396962-0.00010-0 Protein Engineering for Therapeutics, Part B Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Thurber, Greg M. Schmidt, Michael M. Rhoden, John J. Wittrup, Karl Dane Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title | Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title_full | Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title_fullStr | Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title_full_unstemmed | Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title_short | Practical Theoretic Guidance for the Design of Tumor-Targeting Agents |
| title_sort | practical theoretic guidance for the design of tumor targeting agents |
| url | http://hdl.handle.net/1721.1/101376 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0001-7570-2080 |
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