Effective Treatment of Glioblastoma Multiforme With Oncolytic Virotherapy: A Case-Series.

Glioblastoma multiforme (GBM) remains an incurable condition, associated with a median survival time of 15 months with best standard of care and 5-year survival rate of <10%. We report on four GBM patients on combination treatment regimens that included oncolytic virus (OV) immunotherapy, who achieved clinical and radiological responses with long-term survival, thus far, of up to 14 years, and good quality of life. We discuss the radiological findings that provide new insights into this treatment, the scientific rationale of this innovative and promising therapy, and considerations for future research.

Poly(I:C) coated PLGA microparticles induce dendritic cell maturation.

Microparticles from poly(D,L-lactic-co-glycolic acid) [PLGA] are of steadily rising interest for the delivery of antigens to immune cells and the induction of a long-lasting immune response for vaccination or immunological tumor therapy. However, if the desired vaccine contains only weak antigens and fails to activate the antigen presenting cells (APC), the opposite effect, i.e., the induction of immunotolerance may be observed. Therefore, it was the aim of this study to show the ability of protein loaded PLGA microparticles to additionally carry a specific, surface-coated maturation signal to human dendritic cells (DC), i.e., the most potent APC. Polyinosine-polycytidylic acid [poly(I:C)], a ligand of Toll-like receptor (TLR) 3, was efficiently bound either in a single layer or a multilayer attempt to the surface of diethylaminoethyl dextran modified PLGA microparticles. These particles were effectively phagocytized by DC ex vivo and induced a maturation similar to that achieved with a cytokine cocktail or higher concentrations of soluble poly(I:C). In conclusion, the concept of surface coating of biodegradable microparticles with selected TLR ligands might successfully be used in DC-based cell therapies for cancer or in vaccination trials to induce DC maturation and specifically amplify the immunological response to encapsulated antigens.

IFN-y enhances T(H)1 polarisation of monocyte-derived dendritic cells matured with clinical-grade cytokines using serum-free conditions.

Using serum-free conditions, human monocyte-derived dendritic cells (MoDCs) tend to mature insufficiently in a T(H)1-polarizing direction under approved and standardized clinical conditions. However, for the initiation of an efficient tumour antigen-specific cytotoxic T-cell response, the induction of a distinct T(H)1 response is favourable. Therefore, to improve T(H)1 polarisation, the influence of interferon-gamma (IFN-gamma) on the maturation of MoDCs was investigated with clinical-grade cytokines or lipopolysaccharide (LPS) in serum-free medium focusing on the viability, phenotypic characteristics, cytokine profile and restimulating capacities. As in previous research, we confirmed that in respect of viability and phenotypic characteristics, cytokine cocktails consisting of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and prostaglandin (PG) E2, mature MoDCs most efficiently. However, these cytokine-matured MoDCs secreted relatively high levels of IL-10 and only low levels of IL-12p70. Remarkably, if IFN-gamma was added, significantly lower levels of IL-10 concomitant with higher levels of IL-12p70 could be detected. Pretreatment with IFN-gamma did not improve the phenotypic characteristics nor the T(H)1 polarisation of MoDCs. Nevertheless, MoDCs matured with clinical-grade cytokines and IFN-gamma could be re-stimulated most effectively with IFN-gamma. In conclusion, our work demonstrates that addition of INF-gamma to clinical-grade cytokine cocktails readily matures MoDCs and enhances their T(H)1 polarisation efficiently under serum-free conditions.