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.

The present disclosure relates to cells capable of co-expressing T cell receptors (“TCR”) together with membrane-bound IL-15 polypeptides and/or CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified IL-15, IL-15Rα, IL-15/IL-15Rα fusion polypeptide, and IL-15Rα/IL-15 fusion polypeptide sequences, vectors, and associated methods of making and using the same. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods of making and using the same.

Provided are novel fusion proteins, nucleic acids encoding said proteins, vectors comprising said nucleic acids, compositions comprising said nucleic acids or vectors, host cells comprising said nucleic acids, vectors or compositions or pharmaceutical compositions. Provided are methods of reducing (down regulating) a target membrane-bound protein (MBP) level in a cell, methods of producing a cell having a reduced target membrane-bound protein level, or methods of treating a disease, or methods of reducing or preventing GvHD in a subject associated with the administration of one or more CAR T-cells to the subject.

Provided is a method for producing effector cells expressing a desired specificity determining region. In this method, material cells that have a cassette deck structure with a cassette tape gene comprising a gene encoding a marker protein in their genome, wherein the material cells can be differentiated into the effector cells, and wherein the marker protein can be expressed in the effector cells or progenitor cells thereof when the material cells are differentiated into the effector cells or progenitor cells thereof are provided first. The material cells are proliferated, the proliferated cells are differentiated into the effector cells, and then, the gene encoding the marker protein in the effector cells is exchanged with a gene encoding a protein that contribute the desired specificity.

Compositions comprising and methods for the treatment of cancer using a NeoTCR based cell therapy with a secondary Payload in an expression construct.

Claudin 18.2 T cell antigen couplers (TACs) polypeptides having (i) an antigen-binding domain that binds Claudin 18.2, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided. Nucleic acids encoding the claudin 18/2 TACs are also provided.

The present disclosure relates generally to polypeptide constructs, and particularly relate to T-cell receptor (TCR) constructs having binding affinity for a specific cognate antigen. The disclosure also provides compositions and methods useful for producing such constructs as well as methods for the diagnosis, prevention, and/or treatment of conditions associated with cells expressing the cognate antigen recognized by the polypeptide constructs.

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.

The present disclosure provides methods of producing a modified immune cell responsive to orthogonal cytokine signaling and a modified immune cell produced by said method. The present disclosure further provides a modified immune cell responsive to orthogonal cytokine signaling and methods for treating cancer comprising the modified immune cell.

Immune cells, including T cells, expressing a chimeric antigen receptor targeted to CD45 are described. In some cases, the immune cells lack a functional CD45 gene. In some cases, the immune cells also include a modification (a suicide sequence) that allows the cells to be killed in vivo. The immune cells are useful for treating a variety of cancers.