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

Disclosed herein are methods and devices for stimulating an immune response to a disease in a subject, which involves passing sub-microsecond long pulses of electric fields having an amplitude between 5 kV / cm and 68 kV / cm through an abnormal growth of a subject sufficient to suppress myeloid-derived suppressor cell (MDSC) or regulatory T cell (Treg) production, increase adenosine triphosphate (ATP) or high mobility group box 1 (HMGB1) production, or stimulate dendritic cell activation in the subject.

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.

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.

The invention provides for methods of modulating a population of myeloid-derived suppressor cells (MDSCs) in a subject, for treating an autoimmune disease, and also treating cancer in a subject in need thereof. The methods comprise administering to the subject a therapeutically effective amount of an agent that modulates the Tim-3 pathway. The Tim-3 pathway can be activated by a Tim-3 ligand, galectin-9, whereby MDSCs are expanded, or inhibited by an antibody to Tim-3, wherein the expansion of MDSCs is inhibited.

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 MD-SCs 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.

The invention relates to an ionizable cation lipid compound in the technical field of gene treatment and application thereof. The invention further relates to a lipid prepared from the ionizable cation lipid compound; and the application refers to that the lipid is used as a gene drug carrier transporting system. After the lipid prepared from the ionizable cation is compounded with the gene drug siRNA, a compound which is small in grain size and uniform in distribution can be formed. Meanwhile, the ionizable cation lipid compound is electroneutral in an environment with pH of 7.0, in-vivo stability of the lipid compound is increased, and cell toxicity caused by too many positive charges is reduced. The lipid provided by the invention can be modified by lipid polypeptides specifically combined by myeloid derived suppressor cells (MDSCs), and can transfer fluorescent gene drugs in vitro to enter MDSCs.

In certain embodiments, the invention includes therapeutic methods of using a BTK 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.

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.

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.

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) byrostatin 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.

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).

A population of myeloid-derived suppressor cells and the culture procedure to obtain these in vitro starting with bone marrow cells of mice, other animals and human beings, in the presence of specific cytokine combinations used to determine concentrations, is provided.

A method of obtaining a population of cells enriched in human polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) comprises isolating from a cell suspension those cells which express LOX-1 to provide a population of cells enriched with PMN-MDSCs. A method of monitoring the population of LOX-1+ cells in a cell-containing biological sample is useful for determining the efficacy of treatment or the metastasis or increasing progression of cancer. Other cell isolation and diagnostic methods are also described. A composition for use in diagnosing and treating cancer related to PMN-MDSC is provided that contains antagonists and / or inhibitors of genes related to the ER stress response.

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.

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.

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.

The present disclosure is directed to antibodies that bind to DC-HIL on the surface of myeloid-derived suppressor cells, and thus antagonize the T cell suppressor function of these cells, as well as their use in diagnosing and treating cancers such as melanoma.

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.

A cancer vaccine technology is provided which knocks out expression of cell surface immune checkpoint proteins, to facilitate their processing by immune cells, and optionally by knocking-in the expression of cytokines to boost immune response. Non-replicating tumor cells lacking cell surface CD47 are highly effective immunizing agents against subcutaneous mouse melanoma. Whole-cell vaccines inhibited tumor growth, and immunophenotyping showed a dramatic increase in activated effector cell subsets and M1-type macrophages aided by a significant reduction in the tumor-associated macrophage and myeloid derived suppressor cell compartments. A remarkable downregulation of cell surface CD47 was observed in the tumors that did escape after vaccination with genetically modified cells, suggesting the intricate involvement of CD47 in a prophylactic situation. An effective vaccination strategy to increase tumor-specific immune response in solid tumors is provided to improve the outcome of cancer immunotherapy.

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.

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.

A method of obtaining a population of cells enriched in human polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) comprises isolating from a cell suspension those cells which express LOX-1 to provide a population of cells enriched with PMN-MDSCs. A method of monitoring the population of LOX-1+ cells in a cell-containing biological sample is useful for determining the efficacy of treatment or the metastasis or increasing progression of cancer. Other cell isolation and diagnostic methods are also described.

The invention relates to the technical field of medicine and relates to a use of cis-platinum and particularly relates to a use of cis-platinum in high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer treatment and a treatment method. In-vitro experiment and in-vivo animal experiment results show that the amount of G-MDSC in a bladder cancer focus is significantly increased than that of G-MDSC in a paracancerous control group and the amount of CD8+T in a bladder cancer focus is reduced than that of CD8+T in the control group so that an immunosuppressive microenvironment is induced and formed and the establishment and growth of bladder cancer are promoted. The cis-platinum chemotherapy can significantly inhibit the progress of bladder cancer caused by abnormal increasing of G-MDSC and can be further used for high level G-MDSC bladder cancer treatment.

The invention belongs to the field of cytobiology and molecular biology and the field of clinical application, and relates to application of HOXA1. The invention discloses application of the HOXA1 in preparation of an antitumor drug, in particular application in preparation of a drug for suppressing the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). The application shows that the HOXA1 can control the immunosuppressive effect of the MDSCs under a tumor condition; compared with the HOXA1 expression in a para-carcinoma tissue, the HOXA1 expression in the tumor tissue-derived MDSCs of a lung cancer patient is obviously down-regulated. A further experiment shows that by use of an HOXA1 overexpression carrier, in case of HOXA1 overexpression, growth of a tumor in a tumor-bearing mouse can be effectively delayed, and a Th1-CTL-mediated antitumor immune response can be promoted.

The invention relates to a method for detecting monocytelike myeloid-derived suppressor cells in human peripheral blood. Used antibodies comprise an antibody APC anti-human CD33 (a), an antibody PE anti-human CD15 (b), an antibody PE-CF594 anti-human HLA-DR (c), an antibody APC-H7 anti-human CD14 (d), an antibody PE-Cy7 anti-human CD45 (e), and an antibody FITC anti-mouse CD11b (f). A flow type sample solution is prepared; the ratio of mo-MDSCs in the flow type sample solution is detected by a flow cytometer. For the detection of mo-MDSCs, the clear number screening range and specific screening range are given. The method has the advantages that the detection is simple, the operation is convenient, and the detection time is short; only a trace amount of peripheral blood sample markers is required, the cost is low, and the method is suitable for being widely popularized; the peripheral blood samples of 151 testing persons are respectively detected by the method; the detected mo-MDSCs ratio values are obviously different in different populations, and the ratio in a breast cancer patient is obviously higher than the ratio in a healthy person and a breast benign tumor patient; the detection results are calculated and analyzed by Graphpad Prism 6 software via a computer, P is smaller than 0.05, the statistic meaning is realized, and the results are scientific and credible.