A mechanistic compartmental model for total antibody uptake in tumors
Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distribut...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/134471 |
| _version_ | 1811074638672822272 |
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| author | Thurber, Greg M Dane Wittrup, K |
| author_facet | Thurber, Greg M Dane Wittrup, K |
| author_sort | Thurber, Greg M |
| collection | MIT |
| description | Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. |
| first_indexed | 2024-09-23T09:53:00Z |
| format | Article |
| id | mit-1721.1/134471 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:53:00Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1344712022-04-01T16:26:07Z A mechanistic compartmental model for total antibody uptake in tumors Thurber, Greg M Dane Wittrup, K Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. 2021-10-27T20:05:09Z 2021-10-27T20:05:09Z 2012 2019-09-13T18:06:20Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134471 Thurber, G. M., and K. Dane Wittrup. "A Mechanisti Compartmental Model for Total Antibody Uptake in Tumors." J Theor Biol (2012). en 10.1016/j.jtbi.2012.08.034 Journal of Theoretical Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Thurber, Greg M Dane Wittrup, K A mechanistic compartmental model for total antibody uptake in tumors |
| title | A mechanistic compartmental model for total antibody uptake in tumors |
| title_full | A mechanistic compartmental model for total antibody uptake in tumors |
| title_fullStr | A mechanistic compartmental model for total antibody uptake in tumors |
| title_full_unstemmed | A mechanistic compartmental model for total antibody uptake in tumors |
| title_short | A mechanistic compartmental model for total antibody uptake in tumors |
| title_sort | mechanistic compartmental model for total antibody uptake in tumors |
| url | https://hdl.handle.net/1721.1/134471 |
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