Intratumoral delivery of tumor antigen-loaded DC and tumor-primed CD4+ T cells combined with agonist α-GITR mAb promotes durable CD8+ T-cell-dependent antitumor immunity

Autor: Zuqiang Liu, Xingxing Hao, Yi Zhang, Jiying Zhang, Cara D. Carey, Louis D. Falo, Walter J. Storkus, Zhaoyang You
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: OncoImmunology, Vol 6, Iss 6 (2017)
Druh dokumentu: article
ISSN: 2162-402X
2162402X
DOI: 10.1080/2162402X.2017.1315487
Popis: The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4+ T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors. Further subcutaneous co-administration of a vaccine consisting of tumor antigen-loaded dendritic cells (DC) failed to improve the antitumor efficacy of this approach. Remarkably, these same three therapeutic agents elicited significant antitumor benefits when the antitumor CD4+ T cells and tumor antigen-loaded DC were co-injected directly into tumors along with intratumoral or intraperitoneal delivery of α-GITR mAb. This latter protocol induced the production of an array of antitumor cytokines and chemokines within the TME, supporting increased tumor-infiltration by antitumor CD8+ T cells capable of mediating tumor regression and extended overall survival.
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