Fabrication and Characterization of Tumor Nano-Lysate as a Preventative Vaccine for Breast Cancer.

Breast cancer is the most common cancer among women in the United States, with late stages associated with the lowest survival rates. The latest stage, defined as metastasis, accounts for 90% of all cancer-related deaths. There is a strong need to develop antimetastatic therapies. TRAIL, or TNF-related apoptosis inducing ligand, has been used as an antimetastatic therapy in the past, and conjugating TRAIL to nanoscale liposomes has been shown to enhance its targeting efficacy. When circulating tumor cells (CTCs) released during metastasis are exposed to TRAIL-conjugated liposomes and physiologically relevant fluid shear stress, this results in rapid cancer cell destruction into cell fragments. We sought to artificially recreate this phenomenon using probe sonication to mechanically disrupt cancer cells and characterized the resulting cell fragments, termed "tumor nano-lysate", with respect to size, charge, morphology, and composition. Furthermore, an in vivo pilot study was performed to investigate the efficacy of tumor nano-lysate as a preventative vaccine for breast cancer in an immunocompetent mouse model.

SMARCA4 biology in alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS.

Prophylactic Cancer Vaccines Engineered to Elicit Specific Adaptive Immune Response.

Vaccines have been used to prevent and eradicate different diseases for over 200 years, and new vaccine technologies have the potential to prevent many common illnesses. Cancer, despite many advances in therapeutics, is still the second leading causes of death in the United States. Prophylactic, or preventative, cancer vaccines have the potential to reduce cancer prevalence by initiating a specific immune response that will target cancer before it can develop. Cancer vaccines can include many different components, such as peptides and carbohydrates, and be fabricated for delivery using a variety of means including through incorporation of stabilizing chemicals like polyethylene glycol (PEG) and pan-DR helper T-lymphocyte epitope (PADRE), fusion with antigen-presenting cells (APCs), microneedle patches, and liposomal encapsulation. There are currently five cancer vaccines used in the clinic, protecting against either human papillomavirus (HPV) or hepatitis B virus (HBV), and preventing several different types of cancer including cervical and oral cancer. Prophylactic cancer vaccines can promote three different types of adaptive responses: humoral (B cell, or antibody-mediated), cellular (T cell) or a combination of the two types. Each vaccine has its advantages and challenges at eliciting an adaptive immune response, but these prophylactic cancer vaccines in development have the potential to prevent or delay tumor development, and reduce the incidence of many common cancers.