Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with aspartic acid. The TCRs may recognize G12D RAS presented by an HLA-DR heterodimer. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 13 with aspartic acid. The TCRs may recognize G13D RAS presented by an HLA-DQ heterodimer. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Provided herein are compositions and methods for preparing T cell compositions and uses thereof, including methods for treating cancer in a subject in need thereof by administering T cells induced with peptides comprising an epitope sequence from a library of epitope sequences, wherein each epitope sequence in the library is matched to a protein encoded by an HLA allele and binds to a protein encoded by an HLA allele of the subject, is immunogenic according to an immunogenic assay, is presented by antigen presenting cells according to a mass spectrometry assay, and stimulates T cells to be cytotoxic according to a cytotoxicity assay.

The present invention relates to the field of immunology and tumor treatment. Specifically, an Ras G12V mutant epitope peptide, an antigen presenting cell expressing the epitope peptide, a tumor vaccine containing same, and a use of the tumor vaccine in preventing or treating a tumor having RAS G12V mutation. The present invention further relates to a T cell receptor (TCR) specifically recognizing an Ras G12V mutant, a conjugate and a fusion protein containing the TCR, an immune cell expressing the TCR, a T cell drug containing same, and a use of the T cell drug in preventing or treating a tumor having RAS G12V mutation.

The present invention relates to tumor antigens encoded in a 5-upstream open reading frame (uORF) within the 5 UTR of different mRNAs. Compositions and peptides comprising such tumor antigens and a virus encoding such tumor antigens are provided. The present invention also relates to the use of such compositions, peptides and viruses in the treatment of cancer.

The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.

Provided are single domain antibodies that bind to GUCY2C, and chimeric antigen receptors comprising same. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating a disease or disorder are also provided.

Disclosed are methods of isolating paired T cell receptor (TCR) alpha and beta chain sequences, or an antigen-binding portion thereof. Also disclosed are methods of automatically identifying the TCR alpha and beta chain V segment sequences and CDR3 sequences of a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation. Methods of preparing a population of cells that express paired TCR alpha and beta chain sequences, or an antigen-binding portion thereof, are also disclosed. Isolated pairs of TCR alpha and beta chain sequences and isolated populations of cells prepared by the methods are also disclosed.

The present invention provides an epitope peptide of a RAS G13D mutant, an antigen presenting cell expressing the epitope peptide, a tumor vaccine containing the antigen presenting cell, and a use of the tumor vaccine in the prevention or treatment of a tumor having RAS G13D mutation. The present invention also provides a T cell receptor (TCR) specifically recognizing a RAS G13D mutant, a conjugate and a fusion protein containing the TCR, an immune cell expressing the TCR, a T cell drug containing the immune cell, and a use of the T cell drug in the prevention or treatment of a tumor having RAS G13D mutation.

Disclosed are methods of isolating paired T cell receptor (TCR) alpha and beta chain sequences, or an antigen-binding portion thereof. Also disclosed are methods of automatically identifying the TCR alpha and beta chain V segment sequences and CDR3 sequences of a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation. Methods of preparing a population of cells that express paired TCR alpha and beta chain sequences, or an antigen-binding portion thereof, are also disclosed. Isolated pairs of TCR alpha and beta chain sequences and isolated populations of cells prepared by the methods are also disclosed.