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Development of a Curative Therapeutic Vaccine (TheraVac) for the Treatment of Big Solid Tumors
Nie, Y.J.; Yang, D.; Trivett, A.; Xin, H.Y.; Han, Zh.; Chen, X.; Oppenheim, J.
2017-10-27
Source PublicationScientific reports
ISSN2045-2322
Pages1-12
AbstractHarnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848. Intratumoral delivery of HMGN1 and R848 plus Cytoxan eradicated large established CT26 tumors. The resultant tumor-free mice were resistant to subsequent challenge with CT26, indicating the generation of CT26-specific protective immunity. This immunotherapeutic regimen caused homing of tumor-infiltrating DC to draining lymph nodes and increased infiltration of T cells into tumor tissues. Cytoxan in this regimen could be replaced by anti-CTLA4) or anti-PD-L1. Importantly, this immunotherapeutic regimen was also curative for large established mouse Renca and EG7 tumors. Thus, we have developed a curative therapeutic vaccination regimen dubbed ‘TheraVac’ consisting of HMGN1 and R848 plus a checkpoint inhibitor, that can, without using exogenous tumor-associated antigen(s), eliminate various large tumors and induce tumor-specific immunity.
KeywordCT26 tumors immunotherapeutic tumor-specific immunity
URLView the original
Language英語English
The Source to ArticlePB_Publication
PUB ID31578
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYang, D.; Oppenheim, J.
Recommended Citation
GB/T 7714
Nie, Y.J.,Yang, D.,Trivett, A.,et al. Development of a Curative Therapeutic Vaccine (TheraVac) for the Treatment of Big Solid Tumors[J]. Scientific reports, 2017, 1-12.
APA Nie, Y.J.., Yang, D.., Trivett, A.., Xin, H.Y.., Han, Zh.., Chen, X.., & Oppenheim, J. (2017). Development of a Curative Therapeutic Vaccine (TheraVac) for the Treatment of Big Solid Tumors. Scientific reports, 1-12.
MLA Nie, Y.J.,et al."Development of a Curative Therapeutic Vaccine (TheraVac) for the Treatment of Big Solid Tumors".Scientific reports (2017):1-12.
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