The toll-like receptor ligands Hiltonol® (polyICLC) and imiquimod effectively activate antigen-specific immune responses in Tasmanian devils (Sarcophilus harrisii)

Patchett, Amanda L.; Tovar, Cesar; Corcoran, Lynn M.; Lyons, A. Bruce; Woods, Gregory M.

doi:10.1016/j.dci.2017.07.004

Cited by 15 publications

(20 citation statements)

References 46 publications

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“…This evidence that similar antibody responses could be achieved with fewer immunizations was used to refine the protocol for the SH trial. Similarly, results from an adjuvant study on captive devils that took place prior to the SH trial influenced the choice of adjuvant used in the SH protocol ( 12 ). A shorter and, therefore, more practical protocol with a promising adjuvant combination was implemented for SH.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, a study was undertaken prior to the SH trial to assess adjuvant effects on the immune responses of devils to the model antigen, keyhole limpet hemocyanin (KLH) ( 12 ). The study used the TLR-7 agonist imiquimod, and polyICLC (Hiltonol ® ) which is more stable than polyIC due to its ribonuclease resistance.…”

Section: Discussionmentioning

confidence: 99%

“…The SH immunization protocol was shortened in light of the NNP trial results. It also incorporated an improved adjuvant combination that was identified between the NNP and SH releases ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

et al. 2018

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Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti-DFTD immunization trials was remarkable, especially as DFTD is hallmarked by its immune evasion mechanisms. Microsatellite analyzes of MHC revealed that some MHC-I microsatellites correlated to stronger immune responses. These trials signify the first step in the long-term objective of releasing devils with immunity to DFTD into the wild.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

et al. 2018

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“…These results support the potential efficacy LFX453 NMC after further testing and refinement. 88 Griffiths et al (Roswell Park Cancer Institute, Buffalo, NY, USA) investigated the safety and therapeutic efficacy of treating myelodysplastic syndrome or acute myeloid leukemia with a DEC-205/NY-ESO-1 fusion protein (CDX-1401) 96,97 with an adjuvant, Hiltonol®, a TLR3 agonist, 98,99 and combined with standard decitabine-based chemotherapy 100 (NCT01834248). In this Phase I study, organized into 4 cycles of chemotherapy and 5 vaccinations, 9 participants receiving 20 mg/m 2 /day decitabine i.v.…”

Section: Completed Clinical Studiesmentioning

confidence: 99%

Trial Watch: Toll-like receptor agonists in cancer immunotherapy

et al. 2018

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Toll-like receptor (TLR) agonists demonstrate therapeutic promise as immunological adjuvants for anticancer immunotherapy. To date, three TLR agonists have been approved by US regulatory agencies for use in cancer patients. Additionally, the potential of hitherto experimental TLR ligands to mediate clinically useful immunostimulatory effects has been extensively investigated over the past few years. Here, we summarize recent preclinical and clinical advances in the development of TLR agonists for cancer therapy.

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“…6 Activation of TLR3 induces the activation of NF-kB and drives cellularapoptosis. 7,8 In our previous study, we found that common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development. 9 TLR3 plays a negative regulatory role in the initiation and progression of human breast cancer cells, at least in part by downregulating the EGFR/ PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

Fan

Zhou²,

Chen

et al. 2019

OncoImmunology

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Toll-like receptor 3 (TLR3) is a viral sensor that induces apoptosis in response to double-stranded RNA (dsRNA). Common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development. However, all of the polymorphisms in the previous study were only markers of the TLR3 gene, not causative polymorphisms. In this study, we performed a case-control study focusing on the relationship between rs5743305 (−926T>A), a single nucleotide polymorphism (SNP) in the promoter region of TLR3, and breast cancer. We found that the genetic variant rs5743305 increased the risk of breast cancer under the dominant and codominant models (dominant model:

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The toll-like receptor ligands Hiltonol® (polyICLC) and imiquimod effectively activate antigen-specific immune responses in Tasmanian devils (Sarcophilus harrisii)

Cited by 15 publications

References 46 publications

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Trial Watch: Toll-like receptor agonists in cancer immunotherapy

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

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