Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors

Abstract

This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91–99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91–99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91–99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91–99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91–99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg). We conclude that GNP-LLO91–99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.

Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy

“…They also produce large numbers of antibodies and kill breast cancer cells via a complement-dependent cytotoxicity-mediated pathway, significantly delaying the growth of breast cancer. Furthermore, GNP-LO91-99, a tumour vaccine prepared using AuNPs as a novel adjuvant and vaccine carrier, has been applied in preclinical studies on advanced melanoma and bladder cancer [ 240 , 241 ]. The GNP-LO91-99 nanovaccine has significant pro-apoptotic and tumour growth inhibitory effects.…”

Vaccine approaches to treat urothelial cancer

“…Gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 nanovaccines), showed a systemic T helper 1-type immune response in TME: increased percentages of CD4+ and CD8+ T cells, B cells, DCs and reduced levels of myeloid-derived suppressor cells and suppressor T cells. 43 In closing, cytokines given as adjuvants, such as IL-2, GM-CSF or IFN, are gaining attention for their immunomodulatory properties. 44 Peptide-based vaccines are versatile, easy to engineer with a low probability of AEs and contamination; however, the adjuvant necessity and the MHC restriction limit its immunogenicity.…”

Nanomedicine for Combination Urologic Cancer Immunotherapy

“…Terán-Navarro et al combined gold glycoside particles (GNP) with 91–99 peptides of the bacterial toxin listeriolysin O (LLO) to produce a GNP-LLO91–99 nano-vaccine. The nano-vaccine blocked the attenuated immunosuppressive state of bladder cancer, increased the number of intra-tumor cytotoxic T cells and DC cells, and decreased the number of immunosuppressive T reg cells and myeloid-derived suppressor cells (MDSC) [ 82 ].…”