The present invention provides a combination therapy which relies on a small molecule immune stimulator—cyclic-di-nucleotide (CDN)—that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes) formulated with allogeneic human tumor cell lines engineered to secrete high amounts of GM-CSF. This combination therapy can provide an ideal synergy of multiple tumor associated antigens, DC recruitment and proliferation, coupled with a potent DC activation stimulus.

The present invention relates to immuno-protected encapsulated cells producing an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor). The cells of the invention are particularly well adapted for providing an active adjuvant or immunomodulator, for example in the context of immunization in humans and animals. These cells can be used for vaccination where they provide the immunomodulator in an active form, in a continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The invention also relates to a vaccine composition comprising immuno-protected encapsulated cells producing an immunomodulator and an antigenic component. The invention also relates to a kit comprising a cell as described and an antigenic component. The strategy of the invention is perfectly suited for both cancer immunotherapy and vaccination against infectious agents.

A humanized monoclonal antibody against the CD34 surface antigen is provided in the present disclosure. The humanized monoclonal antibody includes a light chain variable region and a heavy chain variable region. In which, a nucleotide sequence encoding the amino acid sequence for the light chain variable region comprises a nucleotide sequence which encodes the amino acid sequence of SEQ ID No. 9 or an amino acid sequence with at least 80% sequence identity to the sequence of SEQ ID No. 9, and a nucleotide sequence encoding the amino acid sequence for the heavy chain variable region comprises a nucleotide sequence which encodes the amino acid sequence of SEQ ID No. 10 or an amino acid sequence with at least 80% sequence identity to the sequence of SEQ ID No. 10.

Disclosed is a method of making a proteinase-engineered cancer vaccine or cancer-cell-derived spheres for treating a cancer patient, especially for cancer patients at advanced/metastatic stage. The cancer vaccine comprises dead cancer-cell-derived spheres with unbroken plasma membrane wherein the extracellular proteins and extracellular portion of membrane proteins are cleaved by proteinase digestion. The cancer vaccine may be derived from cancer cell lines or patients' cancer cells or derivatives. Also disclosed is a method of treating a cancer patient by administrating an effective amount of the cancer vaccine or cancer-cell-derived spheres to the patient. The present invention further provides a method of treating multiple diseases in addition to cancers by the cancer-cell-derived spheres, and obtaining cancer-specific immune components from blood of individuals treated with the cancer-cell-derived spheres.

A cyclic dinucleotide analogue, a pharmaceutical composition thereof, and application. A cyclic dinucleotide analogue (I), an isomer thereof, a prodrug, a stable isotope derivative, or a pharmaceutically acceptable salt has the following structure. The cyclic dinucleotide analogue can be used as a regulator of a stimulator of interferon genes (STING) and a related signal path thereof, and can effectively treat and/or relieve multiple types of diseases, including but not limited to malignant tumors, inflammations, autoimmune diseases, and infectious diseases. In addition, the STING regulator can also be used as a vaccine adjuvant.

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This document provides novel compositions and methods utilizing immunomodulating agents that can stimulate or indirectly augment the immune system, or can have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, e.g., to treat disease caused by asthma and chronic inflammation, such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein can inhibit CD8 T cell-mediated cellular immune responses and can, for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.

The present disclosure relates to compositions and methods for treating or preventing a disease or disorder of immunoprivileged tissue. It is described herein that an immunogenic composition which induces production of memory CD4 T cells allows for the access of a therapeutic antibody to the immunoprivileged tissue.

The present disclosure relates to compositions and methods for treating liver cancers, especially hepatocellular carcinoma, using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of liver cancer.

The present invention provides an immunogenic composition comprising, consisting essentially of or consisting of: a) a cell expressing an interferon-β (IFN-β) receptor agonist, and b) a tumour antigen. The invention also provides methods of treatment using said compositions.

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for an HLA-A11-restricted epitope of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) (KRAS.sub.7-16), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), or Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS). Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.