The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

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 application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described.

Compositions, methods and uses of genetically modified NK cells to treat a patient with a tumor are presented. The genetically modified NK cells express a protein complex having an chain and a chain T cell receptor, at least a portion of which is specific to a patient- or tumor-specific neoepitope, or a tumor associated antigen, and at least a portion of CD3, and at least a portion of CD3. The genetically modified NK cells can be administered to a cancer patient to induce, maintain or augment a T cell immune response against the cancer or the tumor.

The present invention provides Claudin-6-specific immunoreceptors (T cell receptors and artificial T cell receptors (chimeric antigen receptors; CARs)) and T cell epitopes which are useful for immunotherapy.

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.

A composition for treating cancer, including synergistic amounts of a primary cell-derived biologic having the cytokines IL-1, IL-2, IL-6, IL-8, TNF-, and IFN-, and a cancer vaccine having at least one antigen. A composition comprising synergistic amounts of the primary cell-derived biologic in combination with at least one adjuvant. A method of treating cancer by administering the composition. A method of reversing immune suppression and gaining immunity to cancer. A method of producing an immune response to an exogenous antigen. A method of enhancing an immune response in a patient by administering the primary cell-derived biologic in combination with at least one adjuvant, and enhancing the immune response of the patient by a synergistic interaction of the primary cell-derived biologic and the adjuvant. A method of increasing function of an immune system.

Provided herein are methods of producing natural killer cells using a two-step expansion and differentiation method. Also provided herein are methods of suppressing tumor cell proliferation, of treating individuals having cancer or a viral infection, comprising administering the NK cells produced by the method to an individual having the cancer or viral infection.

Described herein are compositions and methods for treating cancer through the combination of tumor antigen-pulsed dendritic cells and Dengue Virus. The combination of the two forms of therapeutic intervention provides enhanced tumor cell reduction compared to either alone. The cancer targeted by compositions and methods described herein may be a solid cancer or blood cancer.

Described herein are antigen binding proteins with specificity to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one MAGE-A4 pMHC antigen binding domain. Methods of treating cancer with the same are also described.