Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools
Abstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53R175H (p53R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53R175...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-83871-w |
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| author | Diana Spiegelberg Le-Ann Hwang Khian Hong Pua Sashwini Chandra Kumar Xin Yu Koh Xiao Hui Koh Ram Kumar Selvaraju Kanaga Sabapathy Marika Nestor David Lane |
| author_facet | Diana Spiegelberg Le-Ann Hwang Khian Hong Pua Sashwini Chandra Kumar Xin Yu Koh Xiao Hui Koh Ram Kumar Selvaraju Kanaga Sabapathy Marika Nestor David Lane |
| author_sort | Diana Spiegelberg |
| collection | DOAJ |
| description | Abstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53R175H (p53R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53R175H could prove immensely value. We aimed to evaluate the in vitro and in vivo binding properties of two novel anti-p53R175H monoclonal antibodies and to assess their performance as agents for molecular imaging. In vitro, 125I-4H5 and 125I-7B9 demonstrated long shelf life and antigen-specific binding. Our in vivo study design allowed head-to-head comparison of the antibodies in a double tumor model using repeated SPECT/CT imaging, followed by biodistribution and autoradiography. Both tracers performed similarly, with marginally faster blood clearance for 125I-7B9. Repeated molecular imaging demonstrated suitable imaging characteristics for both antibodies, with the best contrast images occurring at 48 h post-injection. Significantly higher uptake was detected in the mut-p53-expressing tumors, confirmed by ex vivo autoradiography. We conclude that molecular imaging with an anti-p53R175H tracer could be a promising approach for cancer diagnostics and could be further applied for patient stratification and treatment response monitoring of mutant p53-targeted therapeutics. |
| format | Article |
| id | doaj-art-aa60a2a1a8d44989b6e358edb0163d73 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-aa60a2a1a8d44989b6e358edb0163d732025-01-12T12:24:04ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-83871-wTargeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic toolsDiana Spiegelberg0Le-Ann Hwang1Khian Hong Pua2Sashwini Chandra Kumar3Xin Yu Koh4Xiao Hui Koh5Ram Kumar Selvaraju6Kanaga Sabapathy7Marika Nestor8David Lane9Department of Immunology, Genetics, Pathology, Uppsala UniversityDivisions of Cellular & Molecular Research, National Cancer Centre SingaporeInstitute of Molecular and Cellular Biology, ASTARDivisions of Cellular & Molecular Research, National Cancer Centre SingaporeInstitute of Molecular and Cellular Biology, ASTARInstitute of Molecular and Cellular Biology, ASTARPreclinical PET-MRI Platform, Part of Department of Medicinal Chemistry, Uppsala UniversitySchool of Biological Sciences, Nanyang Technological UniversityDepartment of Immunology, Genetics, Pathology, Uppsala UniversityDepartment of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska InstitutetAbstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53R175H (p53R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53R175H could prove immensely value. We aimed to evaluate the in vitro and in vivo binding properties of two novel anti-p53R175H monoclonal antibodies and to assess their performance as agents for molecular imaging. In vitro, 125I-4H5 and 125I-7B9 demonstrated long shelf life and antigen-specific binding. Our in vivo study design allowed head-to-head comparison of the antibodies in a double tumor model using repeated SPECT/CT imaging, followed by biodistribution and autoradiography. Both tracers performed similarly, with marginally faster blood clearance for 125I-7B9. Repeated molecular imaging demonstrated suitable imaging characteristics for both antibodies, with the best contrast images occurring at 48 h post-injection. Significantly higher uptake was detected in the mut-p53-expressing tumors, confirmed by ex vivo autoradiography. We conclude that molecular imaging with an anti-p53R175H tracer could be a promising approach for cancer diagnostics and could be further applied for patient stratification and treatment response monitoring of mutant p53-targeted therapeutics.https://doi.org/10.1038/s41598-024-83871-wCancer diagnosticsMutant p53Intracellular targetsMolecular imaging |
| spellingShingle | Diana Spiegelberg Le-Ann Hwang Khian Hong Pua Sashwini Chandra Kumar Xin Yu Koh Xiao Hui Koh Ram Kumar Selvaraju Kanaga Sabapathy Marika Nestor David Lane Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools Scientific Reports Cancer diagnostics Mutant p53 Intracellular targets Molecular imaging |
| title | Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools |
| title_full | Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools |
| title_fullStr | Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools |
| title_full_unstemmed | Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools |
| title_short | Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools |
| title_sort | targeting mutant p53 evaluation of novel anti p53r175h monoclonal antibodies as diagnostic tools |
| topic | Cancer diagnostics Mutant p53 Intracellular targets Molecular imaging |
| url | https://doi.org/10.1038/s41598-024-83871-w |
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