25 research outputs found
Nanotechnology-Based Strategies for the Diagnosis and Treatment of Intracranial Neoplasms
Controlling the burst release of doxorubicin from polymeric depots via adjusting hydrophobic/hydrophilic properties
EMP-induced BBB-disruption enhances drug delivery to glioma and increases treatment efficacy in rats
Predictability of drug encapsulation and release from propylene carbonate/PLGA microparticles
Functional and cell proliferative properties of an exopolysaccharide produced by Nitratireductor sp. PRIM-31
Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice
Extracellular diffusion quantified by magnetic resonance imaging during rat C6 glioma cell progression
Cargo-free particles of ammonio methacrylate copolymers: From pharmaceutical inactive ingredients to effective anticancer immunotherapeutics
Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma
Intratumoral temozolomide synergizes with immunotherapy in a T cell-dependent fashion.
Despite temozolomide (TMZ) treatment, the prognosis for patients with glioblastoma multiforme is still dismal. As dose escalation of TMZ is limited by systemic toxicity, intratumoral delivery emerges as an attractive treatment modality, which may sustain cytotoxic drug concentrations intratumorally and induce immunogenic cell death. Both clinical and experimental gliomas have responded to immunotherapy, but the benefit of simultaneous chemo- and immunotherapy is inadequately studied. Here, we monitored survival of GL261-bearing C57BL/6 mice following a 3-day treatment with either intratumoral TMZ (micro-osmotic pump, 4.2 mg/kg/day) or systemic TMZ (i.p. injections, 50 mg/kg/day) alone, or combined with immunization using GM-CSF secreting GL261 cells. Peripheral and intratumoral leukocytes were analyzed by flow cytometry and immunohistochemistry. Intratumoral TMZ induced higher survival rate than systemic TMZ (45 vs. 8 %). When T cells were depleted following intratumoral TMZ, the therapeutic effect was completely abrogated (0 % survival). Intratumoral TMZ synergistically increased survival rate of immunized mice (from 25 to 83 %), while systemic TMZ failed (0 %). While systemic TMZ induced a transient leukopenia, intratumoral TMZ and immunotherapy sustained the proliferation of CD8(+) T cells and decreased the number of intratumoral immunosuppressive cells. In conclusion, intratumoral TMZ alone or in combination with immunotherapy could cure glioma-bearing mice, due to attenuation of local immunosuppression and increase in potential effector immune cells