Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer
Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/4/1026 |
| _version_ | 1797569893872173056 |
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| author | Jana Wood Sayeda Yasmin-Karim Romy Mueller Akila N. Viswanathan Wilfred Ngwa |
| author_facet | Jana Wood Sayeda Yasmin-Karim Romy Mueller Akila N. Viswanathan Wilfred Ngwa |
| author_sort | Jana Wood |
| collection | DOAJ |
| description | Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (<i>p</i> = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings. |
| first_indexed | 2024-03-10T20:17:46Z |
| format | Article |
| id | doaj.art-d240358920854275814ce4955bbccba2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:17:46Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d240358920854275814ce4955bbccba22023-11-19T22:26:12ZengMDPI AGCancers2072-66942020-04-01124102610.3390/cancers12041026Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical CancerJana Wood0Sayeda Yasmin-Karim1Romy Mueller2Akila N. Viswanathan3Wilfred Ngwa4Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA 02115, USADepartment of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA 02115, USADepartment of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA 02115, USADepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD 21287, USADepartment of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA 02115, USACurrent treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (<i>p</i> = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.https://www.mdpi.com/2072-6694/12/4/1026cervical cancerabscopal effectin situ vaccinationradiotherapyanti-CD40immunotherapy |
| spellingShingle | Jana Wood Sayeda Yasmin-Karim Romy Mueller Akila N. Viswanathan Wilfred Ngwa Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer Cancers cervical cancer abscopal effect in situ vaccination radiotherapy anti-CD40 immunotherapy |
| title | Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer |
| title_full | Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer |
| title_fullStr | Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer |
| title_full_unstemmed | Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer |
| title_short | Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer |
| title_sort | single radiotherapy fraction with local anti cd40 therapy generates effective abscopal responses in mouse models of cervical cancer |
| topic | cervical cancer abscopal effect in situ vaccination radiotherapy anti-CD40 immunotherapy |
| url | https://www.mdpi.com/2072-6694/12/4/1026 |
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