TY - JOUR
T1 - Single radiotherapy fraction with local anti-cd40 therapy generates effective abscopal responses in mouse models of cervical cancer
AU - Wood, Jana
AU - Yasmin-Karim, Sayeda
AU - Mueller, Romy
AU - Viswanathan, Akila N.
AU - Ngwa, Wilfred
N1 - Funding Information:
Funding: Research reported in this publication was partially supported by the National Institutes of Health under Award Number R01CA239042. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Research reported in this publication was partially supported by the National Institutes of Health under Award Number R01CA239042. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank T.C. Wu (John Hopkins University) for providing TC-1 cell line for non-profit academic research and Michele Moreau (University of Massachusetts, Lowell; Dana-Farber Cancer Institute) for assistance with the small animal radiation research platform (SARRP).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - Abscopal effect
KW - Anti-CD40
KW - Cervical cancer
KW - Immunotherapy
KW - In situ vaccination
KW - Radiotherapy
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U2 - 10.3390/cancers12041026
DO - 10.3390/cancers12041026
M3 - Article
C2 - 32331490
AN - SCOPUS:85083737833
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 4
M1 - 1026
ER -