Targeted microbeads for attraction and induction of specific innate immune response in the tumor microenvironment

Shahar, Ehud; Gorodetsky, Raphael; Gaberman, Elena; Aizenshtein, É. M.; Pitcovski, Jacob

doi:10.1016/j.vaccine.2010.08.083

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…Polymeric solutions, micro-or nano-particulates can be used as effective adjuvants either alone [203] or in a complexed form with antigens [204] and/or other adjuvants [205]. Various polymers have been demonstrated to have such properties, such as polylactic acid (PLA), poly (lactide-co-glycolide) acid (PLGA) [206,207], chitosan [208][209][210][211] or modified chitosan [207], poly(-glutamic acid) (-PGA) [212,213], polypeptides [204], starch [214,215], polystyrene [35,205], polyphosphazene [216], poly (prolylene sulfide) [217], polyethylene glycol [218], alginate [219], and their copolymers [220,221].…”

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

“…Various polymers have been demonstrated to have such properties, such as polylactic acid (PLA), poly (lactide-co-glycolide) acid (PLGA) [206,207], chitosan [208][209][210][211] or modified chitosan [207], poly(-glutamic acid) (-PGA) [212,213], polypeptides [204], starch [214,215], polystyrene [35,205], polyphosphazene [216], poly (prolylene sulfide) [217], polyethylene glycol [218], alginate [219], and their copolymers [220,221]. They enhance immunogenicity through several mechanisms, including enhancement of antigen uptake by dendritic cells (in vitro) [212], maturation of dendritic cells [212], promotion of proliferation of antigen-specific T cells [212], stimulation of both B and T lymphocytes [208], facilitation of activation of dendritic cells [222], viscosity-induced retention of antigens in the vaccination site [210] and controlled release of antigen by particles [223,224].…”

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…Considerations in choosing MP size, shape and composition were previously discussed [34]. In this study, single ligands or their different combinations were attached to ~1.5-µm iron oxide MP.…”

Section: Discussionmentioning

confidence: 99%

“…Purified mIgG was biotinylated using EZ-Link Biotin LC sulfo-NHS (Pierce, Appleton, WI), and lipopolysaccharide (LPS; L-2654, Sigma-Aldrich) was biotinylated using EZ-Link biotin LC hydrazide (Pierce), as previously described [34,37]. The C5a receptor agonist hexapeptide (N-Methyl-Phe)-Lys-Pro-D-Cha-Cha-D-Arg-CO 2 H, described in detail by Konteatis et al [38], was synthesized with the addition of biotin at the C-terminal position (Gen-Script, Piscataway, NJ) and was designated C5a-pep.…”

Section: Preparation Of Immune-stimulating Ligands and Mp Assemblymentioning

confidence: 99%

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Modulating the innate immune activity in murine tumor microenvironment by a combination of inducer molecules attached to microparticles

Shahar

Gorodetsky

Aizenshtein

et al. 2015

Cancer Immunol Immunother

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Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). A promising route to overcome those drawbacks may be by activating innate immune cells (IIC) in the TME, toward tumor destruction. Studies have shown the ability to "re-educate" pro-tumor-activated IIC toward antitumor responses. The current research aims to stimulate such activation using a combination of innate activators loaded onto microparticles (MP). Four inducers of Toll-like receptors 4 and 7, complement C5a receptor (C5aR) and gamma Fc receptor and their combinations were loaded on MP, and their influence on immune cell activation evaluated. MP stimulation of immune cell activation was tested in vitro and in vivo using a subcutaneous B16-F10 melanoma model induced in C57BL6 mice. Exposure to the TLR4 ligand lipopolysaccharide (LPS) bound to MP-induced acute inflammatory cytokine and chemokine activity in vitro and in vivo, with the elevation of CD45(+) leukocytes in particular GR-1(+) neutrophils and F4/80 macrophages in the TME. Nevertheless, LPS alone on MP was insufficient to significantly delay tumor progression. LPS combined with the C5aR ligand C5a-pep on the same MP resulted in a similar inflammation activation pattern. However, interleukin-10 levels were lower, and tumor growth was significantly delayed. Mixtures of these two ligands on separate MP did not yield the same cytokine activation pattern, demonstrating the importance of the cells' dual activation. The results suggest that combining inducers of distinct innate immune activation pathways holds promise for successful redirection of TME-residing IIC toward anti-tumoral activation.

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