Breast cancer is the most common cause of cancer worldwide and is the leading cause of mortality for women across most of the world. Immunotherapy is a burgeoning area of cancer treatment, including for breast cancer; these are therapies that harness the power of the immune system to clear cancerous cells. Toll-like receptor 3 (TLR3) is an RNA receptor found in the endosome, and ligands that bind to TLR3 are currently being tested for their efficacy as breast cancer immunotherapeutics. The current review introduces TLR3 and the role of this receptor in breast cancer, and summarizes data on the potential use of TLR3 ligands, mainly polyinosinic:polycytidylic acid and its derivatives, as breast cancer monotherapies or, more commonly, as combination therapies with chemotherapies, other immunotherapies and cancer vaccines. The current state of TLR3 ligand breast cancer therapy research is summarized by reporting on past and current clinical trials, and notable preliminary in vitro studies are discussed. In conclusion, TLR3 ligands have robust potential in anticancer applications as innate immune stimulants, and further studies combined with innovative technologies, such as nanoparticles, may contribute to their success.

BackgroundOvarian cancer is a leading cause of cancer mortality in women, and only a small percentage of cases are caught at an early stage. Novel treatments with improved e cacy are needed to ght ovarian cancer and to overcome resistance to traditional therapies. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Two ovarian cancer cell lines were tested for their ability to produce an immune response to poly (I:C) delivered using a nanoparticle carrier, a biodegradable phytoglycogen derived from sweet corn, called nanodendrix (NDX). SKOV-3 and OVCAR-3 have been previously identi ed as dsRNA-resistant and dsRNA-sensitive, respectively. ResultsFirstly, NDX was found to effectively bind poly (I:C), at a w/w ratio of 2:1 NDX:poly (I:C), the resulting particles, poly (I:C)-NDX, were tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity and stimulation of the innate immune response. Both cell lines bound poly (I:C)-NDX, as observed using immunocytochemistry. In OVCAR-3 poly (I:C)-NDX caused signi cant cell death, even at concentrations as low as 62.5ng/mL, measured using the cell viability indicator dye alamarBlue; no cell death was observed with poly (I:C) alone across all concentrations, up to 5µg/mL in SKOV-3 and 0.5µg/mL in OVCAR-3. In both OVCAR-3 and SKOV-3, poly (I:C)-NDX stimulated the production of an innate immune chemokine, CXCL10, at the transcript and protein levels, at signi cantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response compared and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no signi cant cell death. ConclusionsPoly (I:C)-NDX represents a robust and multifunctional therapy with demonstrated e cacy against a range of ovarian tumour cells, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.

Background Ovarian cancer is a leading cause of cancer mortality in women, and only a small percentage of cases are caught at an early stage. Novel treatments with improved efficacy are needed to fight ovarian cancer and to overcome resistance to traditional therapies. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Two ovarian cancer cell lines were tested for their ability to produce an immune response to poly (I:C) delivered using a nanoparticle carrier, a biodegradable phytoglycogen derived from sweet corn, called nanodendrix (NDX). SKOV-3 and OVCAR-3 have been previously identified as dsRNA-resistant and dsRNA-sensitive, respectively. Results Firstly, NDX was found to effectively bind poly (I:C), at a w/w ratio of 2:1 NDX:poly (I:C), the resulting particles, poly (I:C)-NDX, were tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity and stimulation of the innate immune response. Both cell lines bound poly (I:C)-NDX, as observed using immunocytochemistry. In OVCAR-3 poly (I:C)-NDX caused significant cell death, even at concentrations as low as 62.5ng/mL, measured using the cell viability indicator dye alamarBlue; no cell death was observed with poly (I:C) alone across all concentrations, up to 5µg/mL in SKOV-3 and 0.5µg/mL in OVCAR-3. In both OVCAR-3 and SKOV-3, poly (I:C)-NDX stimulated the production of an innate immune chemokine, CXCL10, at the transcript and protein levels, at significantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response compared and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no significant cell death. Conclusions Poly (I:C)-NDX represents a robust and multifunctional therapy with demonstrated efficacy against a range of ovarian tumour cells, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.

No abstract