Heat Shock Proteins In Tumors Research Articles

O2-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

Photothermal therapy (PTT) and photodynamic therapy (PDT) have received tremendous attention owing to their great potential for tumor treatment. However, two main issues hamper the antitumor performance of PDT: overexpression of glutathione (GSH) in tumors, which consumes PDT-induced reactive oxygen species (ROS), and hypoxia within the tumor microenvironment. The drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors, both of which result in ineffective treatment. To address these issues, a MnO2 doped nano-delivery system (HTIM-PMs) was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green (ICG) and MnO2 loading. The surface of polymeric micelles was layered with hyaluronan (HA) and transactivator (TAT) peptides to improve active targeting and increase cell penetration. After internalization, HTIM-PMs showed responsiveness to the tumor microenvironment (acid pH, high glutathione, high H2O2). Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO2 and ICG. The released MnO2 further reduced the GSH level and promoted O2 generation, thus enhancing the PDT effect. The PTT-mediated hyperthermia accelerated blood flow, which is beneficial for O2 distribution, and promotes ROS diffusion. These PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of PTT. This promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.

Abstract A109: Exploring neo-antigens and immunological response in GBM patients after individualized Prophage vaccination

Abstract The Prophage therapeutic platform generates an individualized therapeutic cancer vaccine for each patient. The vaccine for a patient is generated by isolating heat-shock proteins (HSPs) from the patient's individual tumor. Tumor HSPs are complexed to the milieu of material in the tumor, such as mutation neo-antigens. We use NGS, bioinformatics, computational immunology, and immuno-monitoring to explore the ‘omics space of GBM tumors and blood from patients treated with Prophage. We find between 104 and 214 non-synonymous mutations per tumor, including mutations in BRCA1 and EGFR, such as EGFRvIII, and large DNA copy number variations. Integrating patient HLA types, we predict mutation immunogenicity and prioritize mutations as neo-antigens. We correlate neo-antigens to clinical response. Using longitudinal blood samples taken pre- and post-vaccination, we explore both spontaneous and vaccine-induced immunogenicity to neo-antigens. Across the tumors, there are no neo-antigens in common, underscoring the need for individualized vaccination. Citation Format: John Castle, Dan Levey, Elise Drouin, Nicholas Wilson, Steven Schoenfeld, Orin Bloch, Jennifer Buell. Exploring neo-antigens and immunological response in GBM patients after individualized Prophage vaccination. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A109.