The invention relates to plasmids capable of expressing a protein targeting immune cells when transformed into a lactic acid bacterial cell, wherein the protein is chosen from the group consisting of murine and human CXCL12 1α; CXCL17 and Ym1. The invention further relates to lactic acid bacteria transformed with a said plasmid, as well as the use of said lactic acid bacteria for wound healing in humans and animals.

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK.sup.−) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

The invention relates to plasmids capable of expressing a protein targeting immune cells when transformed into a lactic acid bacterial cell, wherein the protein is chosen from the group consisting of murine and human CXCL12 1α; CXCL17 and Ym1. The invention further relates to lactic acid bacteria transformed with a said plasmid, as well as the use of said lactic acid bacteria for wound healing in humans and animals.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

The present invention relates to methods and pharmaceutical composition for treating inflammatory diseases. Inflammation is a defence response to tissue damage or infections that requires tight regulation to prevent impaired healing and to avoid excessive damage and/or autoimmunity. Myeloid cells, including macrophages play a key role in tissue repair and undergo major functional changes during the healing processes, switching from an inflammatory state to a pro-repair phenotype. The inventors have found that TAFA4, a chemokine-like protein, has anti-inflammatory and pro-repair properties. This molecule regulates the phenotype of man monocytes and macrophages by promoting their anti-inflammatory and pro-repair functions. TAFA4 increases macrophage their phagocytic capacities and their production of the anti-inflammatory cytokine IL-10. By contrast, TAFA4 down-regulates the production of the pro-inflammatory cytokines IL-6, IL-113, and TNF-α by human macrophages. Importantly, the inventors have also found that a treatment with TAFA4 has anti-inflammatory effects in vivo and protects mice from LPS-induced endotoxic shock. This protective effect is associated with a reduction in inflammatory cytokine levels and an increase in EL-10 production. Finally, they found that TAFA4 can also exert its anti-inflammatory properties on peripheral blood mononuclear cells from COVID-19 patients, independently of the disease severity. Thus, the present invention relates to a TAFA4 polypeptide or a nucleic acid molecule encoding thereof for use in the treatment of inflammatory diseases.

A synthetic peptide provided according to the technology disclosed here includes (1) a CMTM4-TM related sequence; and (2) an amino acid sequence that functions as a cell membrane permeable peptide.
The synthetic peptide has a total number of amino acid residues of 100 or less.

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin.sup.− and/or pagP.sup.−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd.sup.−, purI.sup.−, and msbB.sup.−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The present invention aims to provide a CAR that contains a single-chain antibody capable of specifically binding to GPC3 localized in the cell membrane and is useful for cancer immunotherapy using a CAR-T cell; and an immunocompetent cell expressing such a CAR. A gene encoding a CAR containing: a single-chain antibody that contains specific heavy-chain CDR1 to CDR3 and specific light-chain CDR1 to CDR3, as defined in claim 1, and specifically binds to a human-derived GPC3 polypeptide; a transmembrane region fused to a carboxyl terminus of the single-chain antibody; and an immunocompetent cell activation signaling transduction region fused to a carboxyl terminus of the transmembrane region is produced, and the gene is introduced into an immunocompetent cell. Thereby, a CAR-expressing immunocompetent cell having excellent cytotoxic activity on cancer cells and interferon gamma (IFN-γ) producibility can be produced.

A fusion protein for cancer treatment and a use thereof is disclosed. The fusion protein for preventing or treating cancer of the present invention includes a fusion polypeptide including: an antibody or fragment thereof binding to a tumor-associated antigen; a linker; and a NK cell-inducing protein of CXCL16, wherein a co-administration of the fusion polypeptide along with the NK cells, an immunocyte therapeutic agent, greatly increases an influx of the NK cells into cancer expressing a certain antigen, thereby having a remarkable effect on preventing or treating cancer.