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

Funding Agencies|US Army Medical Research and Material Command from the National Institutes of Health/NCI [W81XWH-07-1-0412, 5U54CA119335]
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.

Saenz, RebeccaUniversity of Calif San Diego, CA 92093 USA (författare)
Bharati, Ila S.University of Calif San Diego, CA 92093 USA (författare)
Seible, DanielUniversity of Calif San Diego, CA 92093 USA (författare)
Zhang, LiangfangUniversity of Calif San Diego, CA 92093 USA (författare)
Esener, SadikUniversity of Calif San Diego, CA 92093 USA (författare)
Messmer, BradleyUniversity of Calif San Diego, CA 92093 USA (författare)
Larsson, MarieLinköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Hälsouniversitetet(Swepub:liu)marla67 (författare)
Messmer, DavorkaUniversity of Calif San Diego, CA 92093 USA (författare)
University of Calif San Diego, CA 92093 USAAvdelningen för mikrobiologi och molekylär medicin (creator_code:org_t)

Av författaren/redakt...: Campbell, Diahnn; Saenz, Rebecca; Bharati, Ila S.; Seible, Daniel; Zhang, Liangfang; Esener, Sadik; visa fler...; Messmer, Bradley; Larsson, Marie; Messmer, Davorka; visa färre...

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