Attenuated Toxoplasma gondii mutants and methods using the same as vaccines in the prevention or treatment pancreatic cancer are provided.

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 object of the present invention is to provide an immunocompetent cell targeting mesothelin. An immunocompetent cell that expresses a cell surface molecule specifically recognizing human mesothelin, interleukin 7 (IL-7), and chemokine (C-C motif) ligand 19 (CCL19) is produced. It is preferred that: the cell surface molecule specifically recognizing human mesothelin should be chimeric antigen receptor (CAR) having single chain antibody, a transmembrane region, and a signaling region that induces the activation of the immunocompetent cell; and the heavy chain variable region and the light chain variable region should be connected via a peptide linker consisting of a 2- to 30-amino acid sequence.

The present invention is directed to ligand like a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8; cell populations expressing such CARs and the use of the cell populations for cancer therapy.

The present invention provides a vaccine composition for treating or preventing cancer expressing VASH2, containing a peptide including an amino acid sequence represented by SEQ ID NO: 4.

The present disclosure provides methods for expanding TIL populations from fine needle aspirates (FN As) or small biopsies which contain low numbers of TILs, using the methods disclosed herein including in a closed system that leads to improved phenotype and increased metabolic health of the TILs in a shorter time period.

Contemplated cancer therapies comprise co-administration of aldoxorubicin with an immune therapeutic composition that preferably comprises a vaccine component and a cytotoxic cell component.

Systems and methods for determining the likely responsiveness of a human cancer subject to a checkpoint blockade immunotherapy regimen are provided. Sequencing reads are obtained from samples from the subject representative of the cancer. A human leukocyte antigen type and a plurality of clones is determined from the sequencing reads. For each clone, an initial frequency X.sub. in the one or more samples is determined and a corresponding clone fitness score of the clone is computed, thereby computing clone fitness scores. Each such fitness score is computed by identifying neoantigens in the respective clone, computing a recognition potential for each neoantigen, and determining the corresponding clone fitness score of the respective clone as an aggregate of these recognition potentials. A total fitness, quantifying the likely responsiveness of the subject to the regimen, is computed by summing the clone fitness scores across the plurality of clones.

Provided are methods for sensitizing gastrin-associated tumors and/or cancers in subjects to inducers of humoral and cellular immune responses. In some embodiments, the methods relate to administering compositions that have anti-gastrin antibodies, gastrin peptides, and/or nucleic acids that inhibit expression of gastrin gene products to subjects. Also provided are methods for preventing, reducing, and/or eliminating the formation of fibroses associated with tumors and/or cancers, and methods for treating gastrin-associated tumors and/or cancers that include administering to subjects in need thereof a first agent that provides and/or induces an anti-gastrin humoral or cellular immune response in the subject and a second agent that includes one or more stimulators of cellular immune responses against the tumors and/or cancers.

An OCTS-based CAR-T vector for treating pancreatic cancer and malignant mesothelioma includes lentiviral skeleton plasmid, human EF1 promoter (SEQ ID NO.14), OCTS chimeric receptor structural domain, and PDL1 single-chain antibody; the OCTS chimeric receptor structural domain consists of CD8 leader chimeric receptor signal peptide (SEQ ID NO.15), PDL1 single-chain antibody light chain VL (SEQ ID NO.16), PDL1 single-chain antibody heavy chain VH (SEQ ID NO.17), MESOTHELIN single-chain antibody light chain VL (SEQ ID NO.18), MESOTHELIN single-chain antibody heavy chain VH (SEQ ID NO.19), antibody Inner-Linker (SEQ ID NO.20), single-chain antibody Inter-Linker (SEQ ID NO.21), CD8 Hinge chimeric receptor linker (SEQ ID NO.22), CD8 Transmembrane chimeric receptor transmembrane domain (SEQ ID NO.23), TCR chimeric receptor T cell activation domain (SEQ ID NO.26) and chimeric receptor co-stimulator domain.