Therapeutic Vaccines for HPV-Associated Malignancies.

Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year.

Examining breast cancer disparities in African Americans with suggestions for policy.

Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. The literature suggests that African American Women (AAW) are more likely to die from the disease each year compared to their White counterparts. A biological basis for this disparity exists-early age of onset, more advanced stage of the disease, more aggressive histological changes, and worse survival.

Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap. Avelumab has demonstrated clinical activity in a range of human cancers and has been approved by the Food and Drug Administration for the therapy of Merkel cell and bladder carcinomas. Preclinical studies have shown this anti-PD-L1 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC).

Modulatory effects of bortezomib on host immune cell functions.

Bortezomib is an inhibitor of the ubiquitin-proteasome proteolytic pathway responsible for intracellular protein turnover. Cellular proteins controlled by this pathway represent a diverse group of potential therapeutic targets, particularly in cancer cells, which exploit this proteasomal pathway to promote their growth and diminish apoptosis. Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects on the host immune responses.

Increased cell surface free thiols identify effector CD8+ T cells undergoing T cell receptor stimulation.

Recognition of peptide Major Histocompatibility Complexes (MHC) by the T cell receptor causes rapid production of reactive oxygen intermediates (ROI) in naïve CD8(+) T cells. Because ROI such as H2O2 are membrane permeable, mechanisms must exist to prevent overoxidation of surface proteins. In this study we used fluorescently labeled conjugates of maleimide to measure the level of cell surface free thiols (CSFT) during the development, activation and differentiation of CD8(+) T cells.

Development of Proteasome Inhibitors as Therapeutic Drugs.

The proteasome is a multi-unit enzyme complex found in the cytoplasm and nucleus of all eukaryotic cells and is responsible for degradation of unneeded or damaged intracellular proteins by proteolysis, a chemical reaction that breaks peptide bonds. Proteasome inhibition presents a promising approach to cancer therapy by targeting the proteasome function in tumor cells. Delineating the success of bortezomib in the treatment of multiple myeloma and mantle cell lymphoma, this review explores various proteasome inhibitors, currently in development, as molecular targeting agents in the fight against cancer.