The present invention relates to a T cell receptor (TCR) capable of binding to a PRAME peptide having the amino acid sequence SLLQHLIGL (SEQ ID NO: 1) or a portion thereof, or its HLA-A2 bound form. Also encompassed in the present invention is a nucleic acid encoding a TCR, a vector comprising the nucleic acid, and a host cell comprising the TCR, the nucleic acid sequence, or said vector. Comprised is further, a method for obtaining a TCR described herein, a pharmaceutical or diagnostic composition, and a method of detecting the presence of a cancer in a subject in vitro. Furthermore, the present invention relates to the use of a TCR, a nucleic acid and/or a vector for generating modified lymphocytes

Disclosed are uses of NAD+ and/or NAD+ agonists and/or NAD+ inhibitors for preparing a preparation or a kit, and a combination preparation including T cells and NAD+ and/or NAD+ agonists and/or NAD+ inhibitors. The preparation or kit is used for regulating T cell activity, regulating the expression level of CD69 on the surface of T cells, and/or regulating the phosphorylation level in T cells, and/or treating diseases related to T cell activity.

An exemplary combination drug includes (a1) an immunoresponsive cell expressing interleukine-7, CCL19, and a cell surface molecule that specifically recognizes a cancer antigen or (a2) one or more kinds of cells, one or more kinds of nucleic acid delivery vehicles, or a combination thereof, which cooperatively include a nucleic acid encoding interleukine-7 and a nucleic acid encoding CCL19; and (b) an immunosuppression inhibitor, and the drug is for use in treatment of a cancer in a subject. An exemplary immunoresponsive cell expresses interleukin-7, CCL19, an immunosuppression inhibiting polypeptide, and a cell surface molecule that specifically recognizes a cancer antigen.

Cancer immunotherapy has achieved immense clinical success with long survival even in the most difficult to treat cancer. Yet this effect is only observed in a minority and there are no biomarkers of this response. The methods described herein reduce immunosenescence, improve cancer immunotherapy outcomes, vaccination outcomes, and/or treatment of infectious diseases using two independent measures of systemic chronic inflammation (the inflammatory age—iAge—and cytokine response score—CRS) to stratify patients into responders versus non-responders to cancer immunotherapy, vaccination, and/or anti-pathogen therapies. The iAge personalized immune proteome signature creates an individualized initial therapy to reduce iAge and to convert nonresponders patients into responders prior to treatment. Nonresponders can be converted to responders by treating the patients to reduce their iAge and improve their CRS.

Embodiments of the disclosure encompass methods and compositions for producing engineered T cells. The disclosure concerns large-scale processes for producing T cells that may be engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process. The T cells may or may not be viral-specific.

There is provided a pharmaceutical composition for preventing or treating cancer comprising, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor. The fusion protein containing an CD80 fragment, an Fc domain of an immunoglobulin, and an IL-2 variant in an embodiment can activate immune cells such as natural killer cells as well as control the immune cell regulatory activity of regulatory T cells. In addition, the combined administration of the fusion protein and an immune checkpoint inhibitor such as Keytruda known as a PD-1 inhibitor can effectively inhibit cancer. Therefore, a pharmaceutical composition containing, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor can be effectively applied to the treatment of cancer and has high industrial applicability.

There is provided a pharmaceutical composition for preventing or treating cancer comprising, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor. The fusion protein containing an CD80 fragment, an Fc domain of an immunoglobulin, and an IL-2 variant in an embodiment can activate immune cells such as natural killer cells as well as control the immune cell regulatory activity of regulatory T cells. In addition, the combined administration of the fusion protein and an immune checkpoint inhibitor such as Keytruda known as a PD-1 inhibitor can effectively inhibit cancer. Therefore, a pharmaceutical composition containing, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor can be effectively applied to the treatment of cancer and has high industrial applicability.

The present invention provides a novel technology useful for a cancer vaccine therapy, that is, a pharmaceutical composition wherein a Toll-like receptor agonist, LAG-3 protein, a variant thereof or a derivative thereof, at least one immunogenic agent, and an immune checkpoint inhibitor are administered in combination.

The present invention provides a novel technology useful for a cancer vaccine therapy, that is, a pharmaceutical composition wherein a Toll-like receptor agonist, LAG-3 protein, a variant thereof or a derivative thereof, at least one immunogenic agent, and an immune checkpoint inhibitor are administered in combination.

Provided are methods of treating cancer (e.g., a hematological cancer such as myelodysplastic syndrome) that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRPα D1 domain variant and an Fc domain variant in combination with a hypomethylating agent (e.g., azacitidine). Also provided are related kits.