66 results about "Myeloid-derived Suppressor Cell" patented technology

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and / or reduce host immunity and / or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and / or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The invention discloses a ligand polypeptide specifically combined with MDSCs (Myeloid-Derived Suppressor Cells) and a drug delivery system. The ligand polypeptide specifically combined with MDSCs comprises an amino acid sequence as shown in SEQ ID NO.1. The drug delivery system disclosed by the invention comprises the ligand polypeptide, a drug carrying system and at least one active or developing substance, wherein the drug carrying system is specifically lipidosome; the at least one active substance is any substance which is needed to be delivered to a special in-vivo position. The ligand polypeptide disclosed by the invention has good MDSCs-targeting effect, and can be combined with lipidosome to be used as a targeting drug carrier, so that a targeting drug delivery system for tumors is developed.

The invention relates to methods of isolating, culturing, and differentiating myeloid derived suppressor cells (MD-SCs) from embryonic stem (ES) cells and hematopoietic stem cells (HSCs). In certain embodiments, the invention relates to methods and compositions for producing MDSCs from ES cells and HSCs using a combination of factors including macrophage colony-stimulating factor (M-CSF).

The present invention relates to a method for inducing differentiation myeloid-derived suppressor cells from cord blood CD34 positive cells and proliferating the same, and a use of the myeloid-derived suppressor cells. More specifically, myeloid-derived suppressor cells are induced to differentiate and proliferated by culturing cord blood CD34 positive cells in the presence of a cytokine cocktail of GM-CSF and SCF, such that myeloid-derived suppressor cells can be mass-produced in vitro, and the myeloid-derived suppressor cells can be used in preventing or treating immunorejection-related diseases such as graft-versus-host disease.

Methods for the ex vivo generation of cells of the innate (NKT cells and NK cells) and adaptive (T cells) immune systems for use in adoptive cell transfer (ACT) are provided. The NKT cells render T cells resistant to immune suppression (e.g. they are resistant to the effects of myeloid-derived suppressor cells (MDSCs)). The method involves culturing disease-primed immune cells (obtained from a cancer patient or from a patient with an infectious disease) with i) bryostatin and ionomycin (B / I) to activate and differentiate the cells; followed by sequentially culturing the cells with a) a combination of IL-7 and IL-15 and then b) IL-2, to further differentiate the cells and to render them immune resistant. The resistant immune cells are used to treat and prevent cancer and infectious diseases.

In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-δ inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Myeloid derived suppressor cell (MDSC) inhibitory agents and vaccine and / or adjuvant enhancers are provided. Improved vaccine treatment regimens employing these agents are also provided. Cancer vaccines and methods for inhibiting tumor growth and cancer metastases are also presented. The myeloid derived suppressor cell (MDSC) inhibiting agents are described as bisphosphonates (such as liposomal clodronate) and CCR2 inhibitors and / or CCR2 antagonists. Methods for enhancing antibody titer levels in response to an antigen of interest are also provided.

Impressive responses have been observed in patients treated with checkpoint inhibitory anti-PD-1 or anti-CTLA-4 antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Treatment with both anti-PD-1 and anti-CTLA-4 antibodies were unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. However, co-treatment with epigenetic modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of them. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K-inhibitor that reduced circulating MDSCs also cured 80% of mice with metastatic 4T1 tumors when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs.

Compositions and methods for diagnosing and treating tumors using myeloid derived suppressor cells (MDSCs) are provided. More particularly, the compositions contain labeled MDSCs or MDSCs in combination with oncolytic viruses, nano-particles or other anti-tumor agents.

Use of dhS1P and / or PhotoImmunoNanoTherapy as a therapeutic agent is described. Administration of therapeutically effective amounts of dhS1P decrease the number of Myeloid Derived Suppressor Cells and immune suppression in cancer patients. Administration of therapeutically effective amounts of dhS1P can be used as an adjuvant to conventional cancer therapies including immunotherapies. Therapeutic results can be achieved by directly administering dhS1P and / or by indirectly increasing the amount of dhS1P at the tumor site. The therapy permits the patient's immune system to recognize and eliminate cancer cells reducing tumor size and extending patient survival.

The invention provides use of a granulocyte type myeloid derived suppressor cell in the preparation of a diagnostic biomarker for diagnosing and predicting a neoadjuvant chemosensitivity effect of muscle-invasive bladder cancer. The invention further provides use of the granulocyte type myeloid derived suppressor cell in the preparation of a kit for diagnosing and predicting the neoadjuvant chemosensitivity effect of the muscle-invasive bladder cancer. The invention further provides a kit for diagnosing and predicting the neoadjuvant chemosensitivity effect of the muscle-invasive bladder cancer. The kit contains a reagent for detecting the granulocyte type myeloid derived suppressor cell. The invention discovers the granulocyte type myeloid derived suppressor cell as a novel biomarker fordiagnosing and predicting the neoadjuvant chemosensitivity effect of the muscle-invasive bladder cancer. A muscle-invasive bladder cancer patient with low-content granulocyte type myeloid derived suppressor cells can be sequentially subjected to neoadjuvant chemosensitivity and total cystectomy operation, so that the survival rate is increased, the excessive treatment is avoided, and the operationopportunity is not delayed.

Methods for enhancing the suppressive function of myeloid derived suppressor cells (MDSCs) for the treatment of autoimmune diseases using small compounds are disclosed. In certain aspects, the small compounds are glatiramer acetate and mitogen activated protein (MAP) kinase inhibitors. In other aspects, these methods include the administration of exogenous MDSCs or the use of endogenous MDSCs mobilized using stem cell mobilizers. In yet other aspects, compositions containing MDSCs and small compounds of the invention are provided.