Immune Modulating Effects of Poly Iclc

Levy, Hilton B.; Lvovsky, Eduard; Riley, Freddie L.; Harrington, D. G.; Moe, James B.; Hilfenhaus, J.; Stephen, Edward L.

doi:10.1111/j.1749-6632.1980.tb20604.x

Cited by 22 publications

(6 citation statements)

References 3 publications

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“…TLR3 is the receptor for poly-ICLC, a synthetic double stranded RNA shown to increase the antibody response to antigen and augment the activation of NK cells, macrophages, and T-cells ( 125 , 126 ). The North American Brain Tumor Consortium conducted a single-arm phase II trial of patients with recurrent anaplastic glioma, testing 20 mcg/kg poly-ICLC administered three times weekly by intramuscular injection in combination with 200 cGy daily RT to the recurrent brain tumor to a total dose of 60 Gy followed by poly-ICLC for up to 1 year, or until tumor progression.…”

Section: Promotion Of Cross-priming Of Tumor-specific Ctlsmentioning

confidence: 99%

Combinations of Immunotherapy and Radiation in Cancer Therapy

et al. 2014

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The immune system has the ability to recognize and specifically reject tumors, and tumors only become clinically apparent once they have evaded immune destruction by creating an immunosuppressive tumor microenvironment. Radiotherapy (RT) can cause immunogenic tumor cell death resulting in cross-priming of tumor-specific T-cells, acting as an in situ tumor vaccine; however, RT alone rarely induces effective anti-tumor immunity resulting in systemic tumor rejection. Immunotherapy can complement RT to help overcome tumor-induced immune suppression, as demonstrated in pre-clinical tumor models. Here, we provide the rationale for combinations of different immunotherapies and RT, and review the pre-clinical and emerging clinical evidence for these combinations in the treatment of cancer.

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Section: Promotion Of Cross-priming Of Tumor-specific Ctlsmentioning

confidence: 99%

Combinations of Immunotherapy and Radiation in Cancer Therapy

et al. 2014

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“…Because PolyI:C is not stable in the circulation of NHPs and humans, PolyICLC was used in the PP formulation. 37 Both vaccines were well tolerated, with no clinical manifestations more severe than a mild reaction at injection site, no fever, and no elevation in alanine transferase (ALT) levels between days 1 and 7 post vaccination (Supplementary Fig. 11a, b).…”

Section: Resultsmentioning

confidence: 98%

Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity

Bidet

Chu

et al. 2019

npj Vaccines

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Neutralizing antibodies (nAbs) are a critical component for protection against dengue virus (DENV) infection, but little is known about the immune mechanisms governing their induction and whether such mechanisms can be harnessed for vaccine development. In this study, we profiled the early immune responses to flaviviruses in human peripheral blood mononuclear cells and screened a panel of toll-like receptor (TLR) agonists that stimulate the same immune signatures. Monocyte/macrophage-driven inflammatory responses and interferon responses were characteristics of flavivirus infection and associated with induction of nAbs in humans immunized with the yellow fever vaccine YF-17D. The signatures were best reproduced by the combination of TLR agonists Pam 3 CSK 4 and PolyI:C (PP). Immunization of both mice and macaques with a poorly immunogenic recombinant DENV-2 envelope domain III (EDIII) induced more consistent nAb and CD4 + T-cell responses with PP compared to alum plus monophosphoryl lipid A. Induction of nAbs by PP required interferon-mediated signals in macrophages in mice. However, EDIII + PP vaccination only provided partial protection against viral challenge. These results provide insights into mechanisms underlying nAb induction and a basis for further improving antigen/adjuvant combinations for dengue vaccine development.

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“…Poly(I,C)-LC induced moderate to high levels of serum IFN in rodents [4,[15][16][17], nonhuman primates [14,18] and hu mans [19][20][21][22]. This IFN-inducing activity is believed to result from a decreased sensitiv ity to ribonucleases, since poly(I,C)-LC is 4- to 10-fold more resistant to hydrolysis than the parent compound [14,20,22,23], Fur thermore, poly(I,C)-LC has a significantly longer serum half-life than poly(I,C) in pri mates [14], Poly(I,C)-LC has been administered at doses ranging from 0.5 to 27 mg/m2 in sev eral phase I and phase II trials in patients with various solid tumors or leukemia [13,19,20,[22][23][24][25][26][27][28][29], Toxic reactions have been observed with dose-limiting toxicity as a re sult of hypotension and arthralgia, a reaction that may be related to dosage, the magnitude of IFN induction or both. Our previous stud ies in normal mice revealed a dissociation between the optimal immunomodulatory dose and the maximum tolerated dose (MTD) when poly(I,C)-LC was administered in a dose-escalating fashion [30][31][32], Immunotherapeutic studies directed against mé tastasés have revealed that the optimal ther apeutic dose is also dissociated from the MTD [30], Indeed, in previous studies of the therapeutic activity of poly(I,C)-LC for met astatic disease, it demonstrated a bell-shaped curve of therapeutic activity, suggesting either a toxicity-associated limitation of therapeutic activity or a dose-dependent de pression of the augmentation of effector cell activity.…”

Section: Introductionmentioning

confidence: 99%