Chimeric antigen receptors (CARs) are disclosed, along with nucleic acids and vectors encoding, and recombinant cells comprising such CARs and therapeutic compositions containing any of the foregoing. The CARs may comprise mutations that alter CAR expression, cytotoxicity, or cytokine production. Also provided are methods for using recombinant cells comprising these CARs for immunotherapy, e.g., in treating cancer by the administration of a therapeutically effective amount of one or more of the CAR polypeptides, nucleic acids, vectors, and/or immune cells, e.g., human CAR T cells, described herein optionally in combination with other immune and cancer treatments.

A geneticall engineered cell. The cell expresses an exogenous receptor binding to an antigen, and expresses increased RUNX3 or exogenous RUNX3. Also provided are a use of the cell and a method for treating tumors.

The present disclosure provides immune cells genetically modified to produce two antigentriggered polypeptides, each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. The present disclosure further provides systems comprising two antigen-triggered polypeptides (or nucleic acids encoding same), each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. Also provided are method of killing a target cancer cell, using the described genetically modified immune cells and/or systems. The present disclosure also provides poly specific-immune inducing polypeptides including first and second antigen binding domains specific for first and second antigens, respectively, present on the surface of a target cancer cell.

The invention provides improved strategies, prognostic indicators, compositions, and methods for producing personalized neoplasia vaccines. More particularly, embodiments of the present disclosure relate to the identification of neoplasia-specific neo-epitopes to predict survival and to identify and design subject-specific neo-epitopes, further assessing the identified neo-epitopes encoded by said mutations to identify neo-epitopes that are known or determined, or predicted to engage regulatory T cells and/or other detrimental T cells (including T cells with potential host cross-reactivity and/or anergic T cells), and excluding such neo-epitopes that are known, determined, or predicted) to engage regulatory T cells and/or other detrimental T cells (including T cells with potential host cross-reactivity and/or anergic T cells) from the subject-specific neo-epitopes that are to be used in personalized neoplasia vaccines. The present disclosure further relates to a novel ranking system for determining the optimal subject-specific neo-epitopes that are to be used in personalized neoplasia vaccines.

The present invention relates to a method for the treatment of pancreatic cancer comprising administering to a patient in need thereof a CD40 agonist in combination with dendritic cells loaded with a lysate of mesothelioma cells. A further aspect of the present invention relates to dendritic cells loaded with a lysate of mesothelioma cells for use in the treatment of pancreatic cancer. A last aspect of the present invention relates to a pharmaceutical composition comprising such loaded dendritic cells.

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 present invention relates to a novel immunity-inducing agent for treatment and/or prevention of cancer. Specifically, the present invention relates to an immunity-inducing agent comprising, as an active ingredient, at least one polypeptide having immunity-inducing activity and selected from polypeptides derived from MRAP2 and modified forms thereof, or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing the polypeptide in vivo, and a method for inducing immunity, comprising administering the immunity-inducing agent to a subject.

The present invention relates to a tumour lysate and a pharmaceutical composition for use in the treatment of pancreatic cancer. In one aspect, the invention relates to pharmaceutical composition comprising dendritic cells, loaded with said lysate. In one aspect, the pharmaceutical composition is for use in the treatment of pancreatic cancer.

A method of producing a vaccine for a cancer and/or tumor and stage of interest is disclosed. The method includes identifying a first population of peptides that are immunoreactive with a set of biological samples obtained from a set of test subjects that have been identified as having the cancer and/or tumor of interest, and preparing a cancer vaccine composition for the cancer of interest, wherein the cancer vaccine composition comprises a second population of peptides comprising one or more peptides in the first population or a nucleic acid sequence encoding the one or more peptides, thereby producing the vaccine for the cancer and/or tumor of interest. Also disclosed are vaccine compositions and methods of use thereof.

A system for selecting an immunogenic peptide composition comprising a processor and a memory storing processor-executable instructions that, when executed by the processor, cause the processor to create a first peptide set by selecting a plurality of base peptides, wherein at least one peptide of the plurality of base peptides is associated with a disease, create a second peptide set by adding to the first peptide set a modified peptide, wherein the modified peptide comprises a substitution of at least one residue of a base peptide selected from the plurality of base peptides, and create a third peptide set by selecting a subset of the second peptide set, wherein the selected subset of the second peptide set has a predicted vaccine performance, wherein the predicted vaccine performance has a population coverage above a predetermined threshold, and wherein the subset comprises at least one peptide of the second peptide set.