The present invention relates to improved procoagulant antibodies including bispecific antibodies capable of binding to coagulation Factor IX (FIX) or the activated form thereof Factor IXa (FIXa) and optionally Factor X (FX) and the activated form thereof Factor Xa (FXa) and promoting FX activation by FIXa, antibodies binding their epitopes and methods and composition for treating subjects suffering from a coagulopathy such as haemophilia A.

The present invention is inter alia concerned with an inhibitor selected from the group consisting of a selective KMT9-inhibitor, a selective METTL21A-inhibitor and a selective METTL21B-inhibitor for use in the treatment of cancer. KMT9, METTL21A and METTL21B are characterized herein for the first time as histone methyl transferases, and inhibitors of the same can be used for treating cancer.

Compositions, methods, and kits are provided for producing rejuvenated cytotoxic T cells (CTLs) specific for mutated neo-antigen epitopes expressed on cancerous cells, including epidermal growth factor receptor (EGFR) and KRAS neo-antigen epitopes. Antigenspecific CTLs are rejuvenated by reprogramming them into induced pluripotent stem cells (IPSCs) using Yamanaka factors and redifferentiating them back into CTLs while expanding their numbers. After redifferentiation, the IPSC-derived rejuvenated CTLs retain the antigen specificity of the original CTLs from which they were derived, but have the advantage of having longer telomeres and higher proliferative activity than the original CTLs. Pharmaceutical compositions comprising such IPSC-derived rejuvenated CTLs are useful for treating cancers expressing the mutated neo-antigen epitopes recognized by the original CTLs.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The invention relates to the field of immunotherapy and vaccine treatment of diseased cells via enhancing the immune response to the diseased cells. In the context of the present invention this is done by engineering neo-antigens in cells via oligonucleotide mediated production of aberrant RNA transcripts which, when transcribed in the cell, result in the generation or increased expression of aberrant polypeptides. Extracellular display of these polypeptides, of peptide fragments derived provides antigen epitopes (neoantigen) for detection by the immune system.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

Cancer-testis antigens were simultaneously packaged with CpG adjuvant and incorporated into an E2 nanoparticle platform to increase cancer vaccine efficacy. Also described herein is a combination of checkpoint blockade therapy and the nanoparticle vaccine platform to deliver cancer antigens with adjuvant for treatment of tumors and prevention of future tumors. The nanoparticle vaccine platform includes a protein capsule to which are attached adjuvants in the internal hollow cavity and cancer epitopes to the surface. Whereas single-therapies only increase survival, the combined therapy can both increase survival time as well as prevent tumor development in pre-existing tumor conditions by increasing tumor antigen-specific responses (via the nanoparticle vaccines) while simultaneously blocking checkpoints to remove immune suppression (via immune checkpoint inhibition). Furthermore, tumor rechallenge studies show evidence of T cell memory which can prevent tumor development in some individuals.

The present disclosure provides binding proteins, such as antibodies, that bind beta klotho, including human beta klotho, and methods of their use.

The present invention relates to the field of prophylaxis and therapy of cancer. In particular there is provided a protein Indoleamine 2,3-dioxygenase (IDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of IDO or peptides derived here from or IDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to IDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above. The use of IDO and immunogenic peptide fragments hereof in cancer and infection treatment, diagnosis and prognosis is also provided.