Poly (γ-glutamic acid) based combination of water-insoluble paclitaxel and TLR7 agonist for chemo-immunotherapy

Seth, Anushree; Heo, Min; Lim, Yong Taik

doi:10.1016/j.biomaterials.2014.05.076

Cited by 64 publications

(58 citation statements)

References 47 publications

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“…The tumor antigen released can further specify and direct the immune response generated by Gardi-PLGA-activated DCs. The released tumor antigen is also expected to reach systemic circulation and is speculated to keep a check on tumor metastasis at distant sites by causing immuno-activation as previously reported in a similar study [17]. The activation of tumor-resident APCs (macrophages and DCs) was confirmed by immunohistochemistry (IHC) by using specific markers for macrophages (CD68) and activated DCs (CD83).…”

Section: Resultssupporting

confidence: 55%

“…Combination therapies of TLR-based agonist with other anti-cancer treatment regimens have resulted in encouraging outcomes. TRL7 agonist imiquimod in combination with chemotherapeutic drug paclitaxel has demonstrated improved anti-tumor therapy and immunological memory effect in mouse model [17]. Some studies suggest that combination of chemotherapy with immune-stimulating agents does not influence the anti-tumor efficacy of individual drugs [18].…”

Section: Introductionmentioning

confidence: 99%

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Combining vasculature disrupting agent and toll-like receptor 7/8 agonist for cancer therapy

et al. 2016

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This study evaluates the effect of combination of two different treatment regimens for solid tumor therapy: vasculature targeting agent and immune-stimulation. Poly lactide-co-glycolide (PLGA) nanoparticles were synthesized for intracellular delivery of toll-like receptor (TLR) 7/8 agonist—gardiquimod. Spherical and mono-disperse gardiquimod encapsulated PLGA nanoparticles (Gardi-PLGA), approximately 194 nm in size were formulated. Gardi-PLGA induced immune-stimulation, and vasculature disrupting agent (VDA)—5,6-Dimethylxanthenone-4-acetic acid (DMXAA) was used in combination to assessing the influence on bone marrow derived dendritic cells (BMDCs) and B16-F10 melanoma cells. The combination treatment significantly increased the levels of pro-inflammatory cytokines, indicating their activation in BMDCs, while melanoma cells remained viable. Further, mice melanoma model was established, and DMXAA was administered intraperitoneally and Gardi-PLGA was administered via an intra-tumoral injection. The combination treatments strategy significantly inhibited tumor growth as shown by tumor volume analysis, and the survival rate of the mice was found to be 63.6% (n = 11), after 54 days of tumor inoculation. Immunohistochemical findings of tumor sections treated with DMXAA confirmed the in vivo vasculature disruption. Thus, the inhibition of tumor growth can be attributed to the synergistic effect of immune stimulation caused by DC activation and vasculature disruption.

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Section: Resultssupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Combining vasculature disrupting agent and toll-like receptor 7/8 agonist for cancer therapy

et al. 2016

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“…However, PTX that was dispersed in DW alone aggregated and sedimented due to its hydrophobicity (Figure 2). Based on our previous results, 36 we prepared the HA/PTX complex for the injection of 200 µg of PTX per mouse, resulting in weak anticancer activity.…”

Section: In Vivo Near-infrared Imaging Of the Tumor-draining Lymph Nodesmentioning

confidence: 99%

Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

Heo¹,

Kim²,

Yun³

et al. 2015

IJN

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Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy based on immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) to generate a tumor-associated antigen in the tumor microenvironment. Cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) were used to enhance the T helper (Th) 1 immune response. However, CpG ODNs also induced the secretion of interleukin-10 (IL-10) that reduces the Th1 response and enhances the T helper 2 (Th2) response. Therefore, RNA interference was used to downregulate IL-10 secretion from bone marrow-derived den-dritic cells (BMDCs). For the combined immunomodulation of BMDCs, we fabricated two types of poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) containing CpG ODNs to activate BMDCs via Toll-like receptor 9 (CpG ODN-encapsulated PLGA NPs, PCNs) or a small interfering RNA to silence IL-10 (IL-10 small interfering RNA-encapsulated PLGA NPs, PINs). Treatment of BMDCs with both types of PLGA NPs increased the Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for the effective induction of an antitumor immune response. After primary injection with the HA/PTX complex, the tumor-associated antigen was generated and taken up by tumor-recruited BMDCs. After a secondary injection with immunomodulating PCNs and PINs, the BMDCs became activated and migrated to the tumor-draining lymph nodes. As a result, the combination of chemotherapy using the HA/PTX complex and immunotherapy using PCNs and PINs not only efficiently inhibited tumor growth but also increased the animal survival rate. Taken together, our results suggest that the sequential treatment of cancer cells with a chemotherapeutic agent and immunomodulatory nanomaterials represents a promising strategy for efficient cancer therapy.

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“…[17] At umor rechallenge experiment was performed on the PLL/HA-CpG nanocomplex-treated mice that had completely recovered from the primary tumor challenge to confirm the presence of an antitumor memory response (Figure 3d). Analysis of the tumor volume revealed asignificant inhibition of secondary tumor growth in the mice vaccinated with the PLL/HA-CpG nanocomplexes in contrast to age-matched naïve mice.S uch inhibition in tumor growth explains the generation of systemic tumor-specific immune response in the mice after treatment with PLL/HA-CpG nanocomplex.…”

Section: Methodsmentioning

confidence: 99%

Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response

et al. 2015

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Abstract:We have designed and synthesized linear polymerbased nanoconjugates and nanocomplexes bearing multivalent immunostimulatory ligands and also demonstrated that the synthetic multivalent nanocomplexes led to an enhanced stimulation of immune cells in vitro and antitumor and systemic immune memory response in vivo.W eh ave developed hyaluronic acid (HA)-based multivalent nanoconjugates and nanocomplexes for enhanced immunostimulation through the combination of multivalent immune adjuvants with CpG ODNs (as aT LR9 ligand) and cationic poly(l-lysine) (PLL; for the enhancement of cellular uptake). The multivalent HACpG nanoconjugate efficiently stimulated the antigen-presenting cells and the multivalent PLL/HA-CpG nanocomplex also led to an enhanced cellular uptake as well as continuous stimulation of endosomal TLR9. The mice vaccinated with dendritic cells treated with the multivalent nanocomplex exhibited tumor growth inhibition as well as astrong antitumor memory response.

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Poly (γ-glutamic acid) based combination of water-insoluble paclitaxel and TLR7 agonist for chemo-immunotherapy

Cited by 64 publications

References 47 publications

Combining vasculature disrupting agent and toll-like receptor 7/8 agonist for cancer therapy

Combining vasculature disrupting agent and toll-like receptor 7/8 agonist for cancer therapy

Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response

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