Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells.

Background: Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to improve treatment success. In a recent study, we uncovered that a molecule called QAPHA ((E)-3-(5-((2-cyanoquinolin-4-yl)(methyl)amino)-2-methoxyphenyl)-N-hydroxyacrylamide) has a dual function as both a tubulin polymerization and HDAC inhibitors.

Administration of an AAV vector coding for a P2X7-blocking nanobody-based biologic ameliorates colitis in mice.

Background: The pro-inflammatory ATP-gated P2X7 receptor is widely expressed by immune and non-immune cells. Nanobodies targeting P2X7, with potentiating or antagonistic effects, have been developed. Adeno-associated virus (AAV)-mediated gene transfer represents an efficient approach to achieve long-term in vivo expression of selected nanobody-based biologics.

Capsid-modified adeno-associated virus vectors as novel vaccine platform for cancer immunotherapy.

Immunotherapy has significantly improved treatment outcomes in various cancer entities. To enhance immunogenicity and efficacy, and to further broaden its applicability, co-administration of anti-tumor vaccines is considered as a promising strategy. Here, we introduce adeno-associated virus (AAV) vectors, widely used for gene therapy, as a potent cancer vaccine platform.

Evaluation of nanobody-based biologics targeting purinergic checkpoints in tumor models .

Adenosine triphosphate (ATP) represents a danger signal that accumulates in injured tissues, in inflammatory sites, and in the tumor microenvironment. ATP promotes tumor growth but also anti-tumor immune responses notably the P2X7 receptor. ATP can also be catabolized by CD39 and CD73 ecto-enzymes into immunosuppressive adenosine.

Development of Antibody and Nanobody Tools for P2X7.

Antibodies that recognize the ATP-gated P2X7 ion channel are etablished research tools. Nanobodies correspond to the antigen-binding variable immunoglobulin domain (VHH) of heavy chain antibodies that naturally occur in camelids. Nanobodies display better solubility than the variable domains (VH) of conventional antibodies.

A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 .

On murine T cells, mono-ADP ribosyltransferase ARTC2.2 catalyzes ADP-ribosylation of various surface proteins when nicotinamide adenine dinucleotide (NAD) is released into the extracellular compartment. Covalent ADP-ribosylation of the P2X7 receptor by ARTC2.

Evaluation of P2X7 Receptor Function in Tumor Contexts Using rAAV Vector and Nanobodies (AAVnano).

Adenosine triphosphate (ATP) represents a danger signal that accumulates in injured tissues, in inflammatory sites, and in the tumor microenvironment. Extracellular ATP is known to signal through plasma membrane receptors of the P2Y and P2X families. Among the P2X receptors, P2X7 has attracted increasing interest in the field of inflammation as well as in cancer.

CD11c B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors.

CD11c B cells have been reported to be increased in autoimmune diseases, but they are detected in the blood of healthy individuals as well. We aimed to characterize CD11c B cells from healthy donors by flow cytometry, microarray analysis, and functional assays. Here, we report that CD11c B cells are a distinct subpopulation of B cells, enriched in the memory subpopulation even if their phenotype is heterogeneous, with overexpression of genes involved in B-cell activation and differentiation as well as in antigen presentation.

Novel biologics targeting the P2X7 ion channel.

Targeting the P2X7 ion channel, a danger sensor for extracellular nucleotides, improves outcomes in models of inflammation, cancer, and brain-diseases. Antibodies and nanobodies have been developed that antagonize or potentiate gating of P2X7. Their potential advantages over small-molecule drugs include high specificity, lower off-target effects, and tunable in vivo half-life.