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Induction of tumor regression by intratumoral STING agonists combined with anti–programmed death‐L1 blocking antibody in a preclinical squamous cell carcinoma model
Head & neck, 2017-06, Vol.39 (6), p.1086-1094
2017

Details

Autor(en) / Beteiligte
Titel
Induction of tumor regression by intratumoral STING agonists combined with anti–programmed death‐L1 blocking antibody in a preclinical squamous cell carcinoma model
Ist Teil von
  • Head & neck, 2017-06, Vol.39 (6), p.1086-1094
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2017
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • ABSTRACT Background Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. Methods We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death‐L1 blockade combinatorial therapy in SCCFVII tumor‐bearing C3H/HeOUJ mice undergoing intratumoral injections with RR‐cyclic‐di‐guanine (synthetic CDG), CDG (natural cyclic‐di‐guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control). Results Intratumoral CDN treatment groups showed decreased tumor size and enhanced splenocyte Th1 response when compared to the PBS treatment control group (p < .05). The RR‐CDG tumor microenvironment showed upregulated interferon (IFN)‐γ+CD8+ and programmed death‐L1. Combining programmed death‐L1 blocking antibody with RR‐CDG induced regression of established tumors. Conclusion This study demonstrates the antitumor effects of CDNs in a HNSCC cell line. These preclinical data strongly support the future clinical development of intratumoral CDN in patients with HNSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1086–1094, 2017
Sprache
Englisch
Identifikatoren
ISSN: 1043-3074
eISSN: 1097-0347
DOI: 10.1002/hed.24704
Titel-ID: cdi_proquest_miscellaneous_1879658893
Format
–
Schlagworte
Animals, Antibodies, Neoplasm - drug effects, Antibodies, Neoplasm - immunology, Antitumor activity, Apoptosis, Breast cancer, Carcinoma, Squamous Cell - drug therapy, Carcinoma, Squamous Cell - pathology, CD8 antigen, Cell Survival - drug effects, cyclic dinucleotide (CDN), cyclic‐di‐nucleotides, Death, Disease Models, Animal, Female, Growth rate, Guanine, Head and neck, Head and Neck Neoplasms - drug therapy, Head and Neck Neoplasms - pathology, Immunotherapy, Immunotherapy - methods, Injections, Intralesional, Lymphocytes T, Melanoma, Membrane Proteins - drug effects, Membrane Proteins - immunology, Mice, Mice, Inbred C3H, Programmed Cell Death 1 Receptor - administration & dosage, Programmed Cell Death 1 Receptor - immunology, Random Allocation, Sensitivity and Specificity, Squamous cell carcinoma, Squamous Cell Carcinoma of Head and Neck, stimulator of interferon gene (STING), Tumors

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