This invention provides chimeric antigen receptors (CARs) targeting human EphA3 and dual targeting CARs that bind to human EphA3 and to human mutant epidermal growth factor receptor variant III (EGFRvIII). This invention also relates to CAR-T cells comprising the provided CARs or the dual targeting CARs. Methods for treating a solid tumor cancer by administering the CARs are provided.

The present invention relates to an antigen composition comprising at least one mesothelioma cancer cell associated antigen and a pharmaceutically acceptable carrier for use in the treatment of cancer, in particular mesothelioma, wherein dendritic cells are loaded with said antigen composition and wherein said loaded dendritic cells are administered in combination with one or more checkpoint inhibitors, to patients. The present invention also relates to an antigen composition comprising at least two mesothelioma cancer cell associated antigens and a pharmaceutically acceptable carrier. The present invention further relates to an antigen composition comprising at least two mesothelioma cancer cell associated antigens and a pharmaceutically acceptable carrier, for use as a pharmaceutical, in particular for use in the treatment of mesothelioma.

The present disclosure provides a chimeric antigen receptor (CAR) for activating dendritic cells (DCs) in an immunosuppressive tumor environment. The present disclosure also provides compositions comprising the CAR, polynucleotides encoding the CAR, vectors comprising a polynucleotide encoding the CAR, engineered cells comprising the CAR, and method using the same.

An object of the present invention is to provide a therapeutic strategy in the solid tumor area and a means useful therefor to further advance the clinical application of CAR therapy. There is prepared a gene-modified lymphocyte which expresses a chimeric antigen receptor having an EphrinB2 extracellular domain at the antigen recognition site.

Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.

Embodiments of the disclosure include methods and compositions for enhancing expansion of immune cells for immunotherapy. In particular embodiments, immune cells, such as T-cells, express a constitutively active cytokine receptor in which the transmembrane and endodomains are able to provide an activating signal separately from any input to the corresponding exodomain to which they are operably linked. In specific embodiments, the transmembrane and endodomain from IL-7R? is utilized with the exodomain of CD34.

Embodiments concern methods and/or compositions related to immunotherapy for cancer. In particular embodiments, engager immune cells harbor a vector that encodes a secretable engager molecule. In particular cases, the engager molecule has an activation domain and an antigen recognition domain. In some embodiments, the engager molecules further comprise a cytokine or co-stimulatory domain, for example.

The present invention relates to a monobody-based chimeric antigen receptor. The monobody-based chimeric antigen receptor possesses an extracellular ligand binding domain comprising a monobody. In addition, the present invention relates to an immune cell having the monobody-based chimeric antigen receptor expressed on the cell surface membrane thereof. Such monobody-based CAR-immune cells 1) can target a receptor expressed on the surface of cancer cells to exhibit an excellent prophylactic or therapeutic effect on cancer, 2) when administered into humans, exhibit low immunogenicity because they use a human FN3-based monobody as an extracellular ligand binding domain, as opposed to animal-derived scFv-based CAR-immune cells, 3) are of high infiltration into tissues due to their smaller sizes than those of scFV, 4) can minimize the side effects that conventional antibody cancer therapy possesses (e.g., development of an autoimmune disease due to non-specific binding), and 5) can be prepared into various types from a pre-constructed monobody library to various cancer cell antigens. Thus, the monobody-based CAR-immune cells can be advantageously used for preventing or treating incurable solid cancer having various antigens.

The present disclosure provides methods and compositions for producing mitochondria replaced T cells from exhausted T cells, that involves reducing exhausted T cells mitochondrial DNA (mtDNA) and incubating with isolated exogenous mitochondria for a sufficient period of time to generate mitochondria replaced T cells in which expression of at least one exhaustion marker is altered by at least 5%, at least 10%, 20% (e.g., at least 1.25 fold), at least 30%, at least 40%, at least 50%, at least 60%, or more, wherein the mitochondria replaced T cells have improved effector function relative to the exhausted T cells. In addition, the present disclosure also provides methods of treating or ameliorating an age-related disease (e.g., cancer or an autoimmune disease), as well as methods for ameliorating a symptom of a chronic infection (e.g., a chronic viral infection), that involve administering the mitochondria replaced T cells.

EphA2 T-cell epitope are provided herein. The epitopes include peptides corresponding to specific fragments of human EphA2 protein containing one or more T-cell epitopes, and conservative derivatives thereof. The EphA2 T-cell epitopes are useful in an assay, such as an ELISPOT assay, that may be used to determine and/or quantify a patient's immune responsiveness to EphA2. The epitopes also are useful in methods of modulating a patient's immune reactivity to EphA2, which has substantial utility as a treatment for cancers that overexpress EphA2, such as renal cell carcinoma (RCC). The EphA2 epitopes also can be used to vaccinate a patient against EphA2, by in vivo or ex vivo methods.