Disclosed herein are compositions, uses, and methods for treatment of prostate cancers. In one aspect, disclosed herein is a composition or medical preparation comprising at least one RNA, wherein the at least one RNA encodes the following amino acid sequences: (i) an amino acid sequence comprising Kallikrein-2 (KLK2), an immunogenic variant thereof, or an immunogenic fragment of the KLK2 or the immunogenic variant thereof; (ii) an amino acid sequence comprising Prostate Specific Antigen (PSA), an immunogenic variant thereof, or an immunogenic fragment of the PSA or the immunogenic variant thereof; (iii) an amino acid sequence comprising Prostatic Acid Phosphatase (PAP), an immunogenic variant thereof, or an immunogenic fragment of the PAP or the immunogenic variant thereof; (iv) an amino acid sequence comprising Homeobox B13 (HOXB13), an immunogenic variant thereof, or an immunogenic fragment of the HOXB13 or the immunogenic variant thereof; and (v) an amino acid sequence comprising NK3 Homeobox 1 (NKX3-1), an immunogenic variant thereof, or an immunogenic fragment of the NKX3-1 or the immunogenic variant thereof.

Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.

The present invention relates to a recombinant virus of the family Paramyxoviridae comprising an expressible polynucleotide encoding at least one of (i) a tumor antigen, (ii) a fragment of a tumor antigen, and (iii) a variant of (i) or (ii). The present invention further relates to a polynucleotide encoding said recombinant virus of the family Paramyxoviridae and to a host cell comprising said recombinant virus of the family Paramyxoviridae and/or said polynucleotide encoding said recombinant virus of the family Paramyxoviridae. Moreover, the present invention relates to a method for activating immune cells with antitumor activity in a sample comprising cancer cells and to further means, methods, and uses related to the present invention.

The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

The present invention provides the combination of TLR3 agonist and TLR9 agonist can be used to increase the anti-tumor immune response to vaccines, particularly nucleic acid vaccines. Methods of treating cancer and inducing anti-tumor immune responses by treating with a TLR3 agonist and a TLR9 agonist in combination with administration of an anti-tumor vaccine are provided. The TLR3 agonist, TLR9 agonist and the vaccine may be co-administered in a unitary composition or the agonists may be administered in advance of the vaccine.

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.

Disclosed herein are methods of treating or preventing prostate cancer in a subject, the methods comprising administering to the subject a treatment regimen comprising two or more vaccines comprising a great ape adenovirus serotype 20 (GAd20) virus that, in turn, comprises a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 1 and one or more vaccines comprising a Modified Vaccinia Ankara (MVA) virus that, in turn, comprises a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 3 to thereby treat or prevent the prostate cancer.

Disclosed herein are methods of treating or preventing prostate cancer in a subject, the methods comprising administering to the subject a treatment regimen comprising two or more vaccines comprising a great ape adenovirus serotype 20 (GAd20) virus that, in turn, comprises a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 1 and one or more vaccines comprising a Modified Vaccinia Ankara (MVA) virus that, in turn, comprises a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 3 to thereby treat or prevent the prostate cancer.

In various embodiments methods of producing a cell population enriched for CLEC9A+ dendritic cells are provided where the methods involve culturing stem cells and/or progenitor cells in a cell culture comprising culture medium, a notch ligand, stem cell factor (SCF), FLT3 ligand (FLT3L); thrombopoietin (TPO); and IL-3 and/or GMCSF.

Disclosed herein is a method for treating a subject having, or at risk of having, a cancer, comprising administering to the subject a therapeutically effective amount of a tumor membrane vesicle (TMV) and a metformin. In some embodiments, the TMV comprises a B7-1 and/or IL-12 molecule anchored to a lipid membrane (e.g., by a GPI anchor). In some embodiments, the methods can further comprise administering an immune checkpoint inhibitor. The methods are useful for reducing tumor size and metastasis, and in improving anti-tumor immune responses.