Intratumoral administration of the Toll-like receptor 7/8 agonist 3M-052 enhances interferon-driven tumor immunogenicity and suppresses metastatic spread in preclinical triple-negative breast cancer
Damien J Zanker, Alex J Spurling, Natasha K Brockwell, Katie L Owen, Jasmine M Zakhour, Tina Robinson, Hendrika M Duivenvoorden, Paul J Hertzog, Stefanie R Mullins, Robert W Wilkinson, Belinda S Parker
CLINICAL & TRANSLATIONAL IMMUNOLOGY | WILEY | Published : 2020
Objectives: Loss of tumor-inherent type I interferon (IFN) signalling has been closely linked to accelerated metastatic progression via decreased immunogenicity and antitumor immunity. Previous studies in murine models of triple-negative breast cancer (TNBC) demonstrate that systemic IFN inducers are effective antimetastatic agents, via sustained antitumor CD8+ T-cell responses. Repeated systemic dosing with recombinant IFNs or IFN inducers is associated with significant toxicities; hence, the use of alternate intratumoral agents is an active area of investigation. It is critical to investigate the impact of intratumoral agents on subsequent metastatic spread to predict clinical impact. Meth..View full abstract
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Awarded by Cancer Council Victoria
This work was supported by funding from Cancer Council Victoria (Grant-in-aid APP1127757; BS Parker), AstraZeneca and the Victorian Cancer Agency (Fellowship to BS Parker).