The present disclosure is directed to compositions and methods of treating Triple Negative Breast Cancer (TNBC) in a human subject. A method of treating TNBC in a human subject includes administering a therapeutically effective amount of a neoantigen vaccine composition comprising a fusion protein comprising at least one TNBC-associated neoantigen epitope joined to a mutant ubiquitin protein, or a nucleic acid molecule encoding such a protein.

The present invention relates to a method and system for identifying and validating pairs of candidate antigens and their cognate antigen-specific T lymphocytes that are useful for validating the immunogenic activity of paired antigen and TCR sequences. The method includes, inter alia, steps of determining one or more splice variants that are more highly transcribed in a sample obtained e from cohort of patients compared to a reference sample, determining one or more amino acid sequences that occur in an amino acid translation of said one or more splice variants but not in the corresponding splice variant in the reference sample, and predicting HLA binding of the amino acid sequences in order to identify candidate shared antigen. The present invention also relates to methods of characterising and/or treating a medical condition, including cancer.

T cells comprising an engineered genomic modification of the TGFBR2 gene are provided. The genomic modification can reduce receptor surface expression and/or reduce TGF-β induced signaling, and allows T cells having such TGFBR2 disruption to continue to proliferate and continue to kill target tumor cells even in the presence of physiologically relevant levels of TGF-β. In preferred embodiments, the T cells are further engineered to express a CAR or exogenous TCR. Methods of making the engineered T cells, pharmaceutical compositions comprising populations of such T cells, and methods of treating are also provided.

Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

Provided herein are binding proteins recognizing HA-1 antigen and uses thereof.

Compositions and methods for preparing T cell compositions and uses thereof are described, including methods for treating cancer in a subject in need thereof by administering T cells induced with peptides comprising at least one of KRAS epitope having a sequence GACGVGKSA that binds to a protein encoded by an HLA allele C03:04; or having a sequence GAVGVGKSA that binds to a protein encoded by an HLA allele C03:03 wherein the respective protein encoded by the HLA allele is expressed in a cell of the subject. Also included are immunogenic compositions comprising peptide(s) comprising an epitope described above, or antigen presenting cells loaded with the peptide(s) comprising the epitope.

Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a knockout of the expression of the TET2 gene.

Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

The current disclosure fulfills a need in the art by providing methods and compositions for treating and vaccinating individuals against cancer. Accordingly, aspects of the disclosure relate to an isolated peptide comprising at least 70% sequence identity to a peptide of Table 1. In some embodiments, the peptide comprises at least 6 contiguous amino acids of a peptide of Table 1. Further aspects relate to pharmaceutical compositions comprising the isolated peptide, nucleic acids encoding the peptide, and expression vectors and host cells comprising the nucleic acids of the disclosure. Also provided is an in vitro isolated dendritic cell comprising a peptide, nucleic acid, or expression vector of the disclosure.