Disclosed are immunotherapeutic compositions and the concurrent use of combinations of such compositions for the improved induction of therapeutic immune responses and/or for the prevention, amelioration and/or treatment of disease, including, but not limited to, cancer and infectious disease.

The present disclosure is directed recombinant T cell receptors capable of binding a tyrosinase epitope, a MAGA-A1 epitope, a MART1 epitope, a MAGE-A3 epitope, or an SSX2 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

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.

Described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 19 to 50. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 141 to 272. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 273 to 322. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 354 to 458.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

There is disclosed a peptide capable of inducing an immune response against: a ASTE1-1a frameshift mutant protein, wherein the peptide comprises at least 10 consecutive amino acids of SEQ ID NO: 26; a TAE1β-1a frameshift mutant protein, wherein the peptide comprises at least 10 consecutive amino acids of SEQ ID NO: 27; a KIAA2018-1a frameshift mutant protein, wherein the peptide comprises a immunogenic fragment of one of SEQ ID NOs: 9-12, wherein the fragment comprises at least 8 consecutive amino acids of one of one of SEQ ID NOs: 9-12; or a SLC22A9-1a frameshift mutant protein, wherein the peptide comprises at least 8 consecutive amino acids of one of SEQ ID NOs: 14-18. There is also disclosed a peptide mixture comprising a first and second peptide, each independently selected from one of the peptides described above and a peptide capable of inducing an immune response against a TΘEβE2-1a frameshift mutant protein.

Provided herein are tumor-antigen VGLL1 specific peptides. Also provided herein are methods of generating VGLL1-specific T cells and their use for the treatment of cancer. In addition, the VGLL1-specific peptides may be used as a vaccine.

Provided herein are tumor-antigen VGLL1 specific peptides. Also provided herein are methods of generating VGLL1-specific T cells and their use for the treatment of cancer. In addition, the VGLL1-specific peptides may be used as a vaccine.

The invention pertains to a method for treating a cancer which expresses PRAME using T cells which recognize specific peptide epitopes of PRAME, to a method for producing T cells that target cancer cells expressing PRAME, the peptide epitopes of PRAME themselves and to compositions and methods of treatment using these peptides.