The present disclosure provides for improved methods for expanding tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs in a shorter time period than the traditional methods. TIL cell therapy products can be manufactured which easily meet the target cell dose while maintaining desired T cell phenotype.

The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).

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.

An NK cell showing higher cytotoxic activity is provided. An object of the present invention is to provide a pharmaceutical composition for NK cell therapies expected to be highly effective. The present invention provides an NK cell having the following characteristics of (1) and (2) or a population thereof: (1) the NK cell is CD16-positive, highly expresses CD56, and is CD57-negative, and (2) the NK cell is NKG2C-positive, is NKG2A-negative or lowly expresses NKG2A, and is CD94-positive. The present invention also provides a pharmaceutical composition containing a population of such NK cells, and a therapeutically effective amount of antibodies.

The present invention provides a method of treating a cancer in an individual using activated T cells or PBMCs induced by antigen presenting cells (such as dendritic cells) loaded with a plurality of tumor antigen peptides. The method may further comprise administration of the antigen presenting cells loaded with the plurality of tumor antigen peptides to the individual. The methods may be used singly or in combination with an immune checkpoint inhibitor. Precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual are provided. Methods of preparing the activated T cells, methods of monitoring the treatment, and methods of cloning tumor-specific T cell receptors are further disclosed. An isolated population of cells comprising the activated T cells, as well as compositions and kits useful for cancer immunotherapy are also provided.

Provided herein are methods of isolating and expanding a population of tumor reactive lymphocytes (TRLs) from a fluid sample of a subject in need thereof. In some embodiments, methods of isolating and expanding a population of TRLs comprise flowing the TRLs across a magnetic capture zone of a microfluidic device. Also provided herein are methods of administering a population of TRLs to a subject in need thereof. Also provided herein are compositions comprising therapeutically enhanced TRLs.

Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.

An NK cell showing higher cytotoxic activity is provided. An object of the present invention is to provide a pharmaceutical composition for NK cell therapies expected to be highly effective. The present invention provides an NK cell having the following characteristics of (1) and (2) or a population thereof: (1) the NK cell is CD16-positive, highly expresses CD56, and is CD57-negative, and (2) the NK cell is NKG2C-positive, is NKG2A-negative or lowly expresses NKG2A, and is CD94-positive. The present invention also provides a pharmaceutical composition containing a population of such NK cells, and a therapeutically effective amount of antibodies.

Generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.