The Cellular and Transcriptomic Early Innate Immune Response to BCG Vaccination in Mice.

It is established that BCG vaccination results in the development of both a specific immune response to mycobacterial infections and a nonspecific (heterologous) immune response, designated as trained immunity (TRIM), to other pathogens. We hypothesized that local BCG immunization may induce an early immune response in bone marrow and spleen innate immunity cells. The early transcriptomic response of various populations of innate immune cells, including monocytes, neutrophils, and natural killer (NK) cells, to BCG vaccination was examined.

Non-viral-mediated gene transfer of OX40 ligand for tumor immunotherapy.

Background: Immune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Another way to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators.

Spheroids of FAP-Positive Cell Lines as a Model for Screening Drugs That Affect FAP Expression.

Fibroblast activation protein has a unique expression profile that manifests mainly in wounds and tumors, which anticipates it as an encouraging and selective target for anticancer therapy. However, research of the therapeutic potential of FAP is limited both by legal restraints when working in vivo and by the difficulty of obtaining standardized primary cultures of FAP-positive cancer-associated fibroblasts due to their high heterogeneity. We found that 3D spheroids of FAP-positive cell lines could serve as robust and convenient models of FAP expression, in contrast to monolayers.

Efficiency of Promoters of Human Genes and at Organism Level in a Model.

The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein () and the connective tissue growth factor () can function in tumor-associated stromal cells but are practically inactive in normal adult cells. Accordingly, the promoters of these genes can be used to develop vectors targeted to the tumor microenvironment.

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers.

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous.

Cell-specific expression of the gene is regulated by enhancer elements.

Fibroblast activation protein (FAP) is an integral membrane serine protease that acts as both dipeptidyl peptidase and collagenase. In recent years, FAP has attracted considerable attention due to its specific upregulation in multiple types of tumor cell populations, including cancer cells in various cancer types, making FAP a potential target for therapy. However, relatively few papers pay attention to the mechanisms driving the cell-specific expression of the gene.

Efficient Selection of Enhancers and Promoters from MIA PaCa-2 Pancreatic Cancer Cells by ChIP-lentiMPRA.

A library of active genome regulatory elements (putative promoters and enhancers) from MIA PaCa-2 pancreatic adenocarcinoma cells was constructed using a specially designed lentiviral vector and a massive parallel reporter assay (ChIP-lentiMPRA). Chromatin immunoprecipitation of the cell genomic DNA by H3K27ac antibodies was used for primary enrichment of the library for regulatory elements. Totally, 11,264 unique genome regions, many of which are capable of enhancing the expression of the CopGFP reporter gene from the minimal CMV promoter, were identified.

Possibility for Transcriptional Targeting of Cancer-Associated Fibroblasts-Limitations and Opportunities.

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE).

Searching for Promoters to Drive Stable and Long-Term Transgene Expression in Fibroblasts for Syngeneic Mouse Tumor Models.

Tumor is a complex system of interactions between cancer cells and other cells of the tumor microenvironment. The cancer-associated fibroblasts (CAFs) of the tumor microenvironment remain in close contact with the cancer cells and play an important role in cancer progression. Genetically, CAFs are more stable than cancer cells, making them an attractive target for genetic modification in gene therapy.

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

The failure of therapies directed at targets within cancer cells highlight the necessity for a paradigm change in cancer therapy. The attention of researchers has shifted towards the disruption of cancer cell interactions with the tumor microenvironment. A typical example of such a disruption is the immune checkpoint cancer therapy that disrupts interactions between the immune and the cancer cells.

Activity of the upstream component of tandem TERT/survivin promoters depends on features of the downstream component.

We spliced the promoters of the human telomerase and human survivin genes (PhTERT and PhSurv, respectively) widely used for gene therapy and known to have the broadest cancer type spectrum of activity. Two head-to-tail constructs were obtained: the PhTERT-PhSurv and PhSurv-PhTERT tandems. The splicing caused quantitative and qualitative changes in the promoter features.