The purpose of this research was to investigate the use of biodegradable poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA-NP) as a vaccine delivery system to codeliver antigen, ovalbumin (OVA) along with monophosphoryl lipid A (MPLA) as adjuvant for induction of potent CD4(+) and CD8(+) T cell responses. The primary CD4(+) T responses to OVA/MPLA NP were investigated using OVA-specific T cells from DO11.10 transgenic mice. Following adoptive transfer of these cells, mice were immunized s.c. by NP formulations.

Poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) and newly developed poly(ethylene oxide)-block-poly(alpha-benzyl carboxylate epsilon-caprolactone) (PEO-b-PBCL) micelles were evaluated for the solubilization and delivery of cucurbitacin I and B, poorly water soluble inhibitors of signal transducer and activator of transcription 3 (STAT3). Encapsulation of cucurbitacins in PEO-b-PCL and PEO-b-PBCL by co-solvent evaporation technique resulted in polymeric micelles <90 nm in diameter.

The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect.

This study was conducted to formulate a nonviral delivery system for the delivery of small interfering RNA (siRNA) to B16 melanoma cells in vitro. For this purpose, oleic and stearic acid modified derivatives of branched polyethylenimine (PEI) were prepared and evaluated. The hydrophobically modified polymers increased siRNA condensation up to 3 folds as compared to the parent PEI. The modified PEIs exhibited up to 3-fold higher siRNA protection from degradation in fetal bovine serum as compared to the parent PEI.

Persistent activation of signal transducer and activator of transcription 3 (STAT3) has been shown to impart several oncogenic features in many solid and blood tumors. In this study, we investigated the potential of nanoparticles based on polyethylenimine (PEI) modified with stearic acid (StA), to deliver siRNA for efficient STAT3 downregulation in B16 melanoma cells. The B16 cells were targeted with approximately 6-200 nm of siRNA complexes for 36 h.

PURPOSE:

Tumors can escape immune eradication by harnessing dendritic cell (DC) maturation. However, DC types used as in vitro models to study tumor-mediated immunosuppression possess fundamental variability that could influence research outcomes. Therefore, we assessed the behavior of two distinct murine DC models upon exposure to tumor-conditioned medium of B16.F10 melanoma (B16-CM).

METHODS:

In dendritic cells (DCs), the induction of signal transducer and activator of transcription 3 (STAT3) by tumor-derived factors (TDFs) renders DCs tolerogenic and suppresses their antitumor activity. Therefore, silencing STAT3 in DCs is beneficial for cancer immunotherapy. We have shown that STAT3 knockdown in B16 murine melanoma by siRNA polyplexes of polyethylenimine (PEI) or its stearic acid derivative (PEI-StA) induces B16 cell death in vitro and in vivo.

We have previously developed micelles of methoxy poly(ethylene oxide)-b-poly(ε-caprolactone) as vehicles for the solubilization and delivery of cyclosporine A (CsA). These micelles were able to reduce the renal uptake and nephrotoxicity of CsA. The purpose of the current study was to test the efficacy of polymeric micellar formulation of CsA (PM-CsA) in suppressing immune responses by either T cells or dendritic cells (DCs). The performance of PM-CsA was compared to that of the commercially available formulation of CsA (Sandimmune®).

Persistent activation of STAT3 plays a major role in cancer progression and immune escape. Therefore, targeting STAT3 in tumors is essential to enhance/reactivate antitumor immune response. In our previous studies, we demonstrated the efficacy of stearic acid-modified polyethylenimine (PEI-StA) in promoting small interfering RNA (siRNA) silencing of STAT3 in B16.F10 melanoma in vitro and in vivo. In the current study, we examine the immunologic impact of this intervention.