Sialyl-Tn serves as a potential therapeutic target for ovarian cancer
Abstract Background Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-04-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-024-01397-1 |
| _version_ | 1797219669082374144 |
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| author | Linah Al-Alem Jillian M. Prendergast Justin Clark Bianca Zarrella Dominique T. Zarrella Sarah J. Hill Whitfield B. Growdon Venkatesh Pooladanda David R. Spriggs Daniel Cramer Kevin M. Elias Rawan I. Nazer Steven J. Skates Jeff Behrens Daniel T. Dransfield Bo R. Rueda |
| author_facet | Linah Al-Alem Jillian M. Prendergast Justin Clark Bianca Zarrella Dominique T. Zarrella Sarah J. Hill Whitfield B. Growdon Venkatesh Pooladanda David R. Spriggs Daniel Cramer Kevin M. Elias Rawan I. Nazer Steven J. Skates Jeff Behrens Daniel T. Dransfield Bo R. Rueda |
| author_sort | Linah Al-Alem |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. Methods We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. Results Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. Conclusions Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective. |
| first_indexed | 2024-04-24T12:37:19Z |
| format | Article |
| id | doaj.art-6ed8e2117ab34255a0bb41fc39805f9e |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-24T12:37:19Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-6ed8e2117ab34255a0bb41fc39805f9e2024-04-07T11:27:10ZengBMCJournal of Ovarian Research1757-22152024-04-0117111610.1186/s13048-024-01397-1Sialyl-Tn serves as a potential therapeutic target for ovarian cancerLinah Al-Alem0Jillian M. Prendergast1Justin Clark2Bianca Zarrella3Dominique T. Zarrella4Sarah J. Hill5Whitfield B. Growdon6Venkatesh Pooladanda7David R. Spriggs8Daniel Cramer9Kevin M. Elias10Rawan I. Nazer11Steven J. Skates12Jeff Behrens13Daniel T. Dransfield14Bo R. Rueda15Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalSiamab Therapeutics, IncSiamab Therapeutics, IncVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalDepartment of Medical Oncology, Dana-Farber Cancer InstituteVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalDivision of Hematology-Oncology, Massachusetts General HospitalObstetrics and Gynecology Epidemiology Center, Brigham and Women’s HospitalDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women’s HospitalSiamab Therapeutics, IncBiostatistics Center, Massachusetts General HospitalSiamab Therapeutics, IncSiamab Therapeutics, IncVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General HospitalAbstract Background Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. Methods We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. Results Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. Conclusions Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.https://doi.org/10.1186/s13048-024-01397-1Sialyl-TnOvarian cancerCompanion diagnosticTargeted therapy |
| spellingShingle | Linah Al-Alem Jillian M. Prendergast Justin Clark Bianca Zarrella Dominique T. Zarrella Sarah J. Hill Whitfield B. Growdon Venkatesh Pooladanda David R. Spriggs Daniel Cramer Kevin M. Elias Rawan I. Nazer Steven J. Skates Jeff Behrens Daniel T. Dransfield Bo R. Rueda Sialyl-Tn serves as a potential therapeutic target for ovarian cancer Journal of Ovarian Research Sialyl-Tn Ovarian cancer Companion diagnostic Targeted therapy |
| title | Sialyl-Tn serves as a potential therapeutic target for ovarian cancer |
| title_full | Sialyl-Tn serves as a potential therapeutic target for ovarian cancer |
| title_fullStr | Sialyl-Tn serves as a potential therapeutic target for ovarian cancer |
| title_full_unstemmed | Sialyl-Tn serves as a potential therapeutic target for ovarian cancer |
| title_short | Sialyl-Tn serves as a potential therapeutic target for ovarian cancer |
| title_sort | sialyl tn serves as a potential therapeutic target for ovarian cancer |
| topic | Sialyl-Tn Ovarian cancer Companion diagnostic Targeted therapy |
| url | https://doi.org/10.1186/s13048-024-01397-1 |
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