{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:00:11Z","timestamp":1783044011604,"version":"3.54.6"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA239042"],"award-info":[{"award-number":["R01CA239042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 (p = 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.<\/jats:p>","DOI":"10.3390\/cancers12041026","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-0425","authenticated-orcid":false,"given":"Jana","family":"Wood","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 04181 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayeda","family":"Yasmin-Karim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-8914","authenticated-orcid":false,"given":"Romy","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akila N.","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Ngwa","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/ijgo.12611","article-title":"Cancer of the cervix uteri","volume":"143","author":"Bhatla","year":"2018","journal-title":"Int. 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