| 1. |
- Campbell, Diahnn, et al.
(författare)
-
Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D, L-lactic-co-glycolic) acid nanoparticles nanoparticles
- 2015
-
Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 17:48
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as potent immune adjuvant. Method In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2) positive breast cancer. Results Free peptide did not significantly augment immune responses but, when delivered in poly(D, L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2 specific T cells was observed in vitro. Vaccination of HER2NEU transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91 loaded PLGA-NPs enhanced the activation of HER2 specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival. Conclusion Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine.
|
|
| 2. |
- Clawson, Corbin, et al.
(författare)
-
Delivery of a peptide via poly(D,L-lactic-co-glycolic) acid nanoparticles enhances its dendritic cell-stimulatory capacity
- 2010
-
Ingår i: NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE. - : Future Medicine. - 1549-9634. ; 6:5, s. 651-661
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) are attractive carriers for vaccines. We have previously shown that a short peptide (Hp91) activates dendritic cells (DCs), which are critical for initiation of immune responses. In an effort to develop Hp91 as a vaccine adjuvant with NP carriers, we evaluated its activity when encapsulated in or conjugated to the surface of poly(D, L-lactic-co-glycolic) acid (PLGA) NPs. We found that Hp91, when encapsulated in or conjugated to the surface of PLGA-NPs, not only activates both human and mouse DCs, but is in fact more potent than free Hp91. Hp91 packaged within NPs was about fivefold more potent than the free peptide, and Hp91 conjugated to the surface of NPs was similar to 20-fold more potent than free Hp91. Because of their capacity to activate DCs, such NP-Hp91 systems are promising as delivery vehicles for subunit vaccines against infectious disease or cancer.
|
|
| 3. |
- Saenz, Rebecca, et al.
(författare)
-
TLR4-dependent activation of dendritic cells by an HMGB1-derived peptide adjuvant
- 2014
-
Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 12:211
-
Tidskriftsartikel (refereegranskat)abstract
- High mobility group box protein 1 (HMGB1) acts as an endogenous danger molecule that is released from necrotic cells and activated macrophages. We have previously shown that peptide Hp91, whose sequence corresponds to an area within the B-Box domain of HMGB1, activates dendritic cells (DCs) and acts as an adjuvant in vivo. Here we investigated the underlying mechanisms of Hp91-mediated DC activation. Hp91-induced secretion of IL-6 was dependent on clathrin-and dynamin-driven endocytosis of Hp91 and mediated through a MyD88- and TLR4-dependent pathway involving p38 MAPK and NF kappa B. Endosomal TLR4 has been shown to activate the MyD88-independent interferon pathway. Hp91-induced activation of pIRF3 and IL-6 secretion was reduced in IFN alpha beta R knockout DCs, suggesting an amplification loop via the IFN alpha beta R. These findings elucidate the mechanisms by which Hp91 acts as immunostimulatory peptide and may serve as a guide for the future development of synthetic Th1-type peptide adjuvants for vaccines.
|
|
