Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-l-lysine in carboxymethyl cellulose [Poly(I,C)-LC]

Black, Paul L.; Hartmann, D; Pennington, Robin; Phillips, Hamblin; Schneider, Mark; Tribble, Henry R.; Talmadge, James E.

doi:10.1016/0192-0561(92)90005-6

Cited by 15 publications

(8 citation statements)

References 28 publications

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“…PolyICLC (PICLC) is a clinical grade modified formulation of PIC (stabilized with poly-L-lysine and carboxymethylcellulose [38]) that preserves immunomodulatory activities [37, 39, 40]. It induces mucosal and systemic innate antiviral responses in rhesus macaques [41, 42] and humans [43], has demonstrated safety and anti-neoplastic and IFN-inducing activity in humans, and is actively being developed as an adjuvant for antiviral and anti-cancer vaccines and therapeutics [29, 30, 37, 43–46] as well as a potential HIV latency reversing agent [47].…”

Section: Introductionmentioning

confidence: 99%

PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo

et al. 2016

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Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity.

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Section: Introductionmentioning

confidence: 99%

PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo

et al. 2016

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“…Therefore, intratumorally administered immunostimulating agents, which can create an immunostimulating TME thereby allowing the recruitment of T cells, can be combined with immune checkpoint inhibitors. [101,102]. This in situ vaccination approach combining poly-ICLC with Flt3L and ionizing radiation therapy, is built on previous work in order to improve efficacy.…”

Section: Key Intratumoral Immunotherapymentioning

confidence: 99%

Delivery routes matter: Safety and efficacy of intratumoral immunotherapy

Lombaerde

Wever

Geest

2021

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…The doses of Pam3CSK4 and poly I:C were chosen based on both literature and dose-response studies for the optimal inflammatory responses (data not shown). [84][85][86] Eyes and plasma were collected 0, 8, 24, and 72 hours post injection. C3 and Cfb mRNAs and C3 breakdown products were graphed relative to the average value of PBS-treated controls.…”

Section: Aging Increases Baseline Complement Levels While Decreasing mentioning

confidence: 99%

Induction of Ocular Complement Activation by Inflammatory Stimuli and Intraocular Inhibition of Complement Factor D in Animal Models

Crowley

Delgado

Will-Orrego

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Systemic TLR stimulation and eye tissue injury induced time-dependent alternative complement pathway activation in the eye. Ocular complement levels were also gradually elevated during aging. An anti-FD antibody IVT potently inhibited LPS-induced complement activation in the posterior segment of the eye. This study provides insights into the dynamic profile of ocular complement activation, which is valuable for complement research in eye diseases and for developing complement therapeutics for AMD.

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Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-l-lysine in carboxymethyl cellulose [Poly(I,C)-LC]

Cited by 15 publications

References 28 publications

PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo

PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo

Delivery routes matter: Safety and efficacy of intratumoral immunotherapy

Induction of Ocular Complement Activation by Inflammatory Stimuli and Intraocular Inhibition of Complement Factor D in Animal Models

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