Disclosed herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. Also disclosed herein is use of the immunotherapeutic compositions.

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 valine. The TCRs may recognize G12V RAS presented by HLA-A3. Related poly peptides 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 current disclosure provides polypeptide constructs and cells comprising CDR3 regions of 9. 2 or both, that selectively bind a J-configuration of CD277 on a target cell. The disclosure also provides pharmaceutical compositions with the disclosed polypeptides or cells and methods of using these compositions in the treatment of cancer.

This application relates to methods for overcoming or preventing resistance of a KRAS mutant cancer cell to a growth inhibition and/or cell death induction by a KRAS inhibitor or a SHP2 inhibitor, as well as to methods for enhancing sensitivity of a KRAS mutant cancer cell to a KRAS inhibitor or a SHP2 inhibitor. The application further relates to methods of treating a KRAS mutant cancer in a subject, the method comprising administering to the subject an effective amount of a KRAS inhibitor or a SHP2 inhibitor and an inhibitor of expression or function or a degrader or a binding partner of one or more of various proteins described herein. Related pharmaceutical compositions and kits are also disclosed.

Disclosed herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. Also disclosed herein is use of the immunotherapeutic compositions.

Modified T cells comprising ectopic CD40 proteins (such as chimeric CD40 proteins including a CD40 extracellular domain and a heterologous intracellular domain) are provided. Also provided are compositions, including pharmaceutical formulations, comprising the modified T cells, and methods for increasing T cell-mediated tumor cell-specific cytotoxicity using the same. Methods of treating a subject with cancer including administering to the subject the modified T cells, thereby activating an innate immune response and/or an adaptive immune response in the subject are also provided.

The present disclosure provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

The present disclosure provides compositions and methods for targeting a neoantigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as T cell receptors bind to a neoantigen:HLA complex. Disclosed binding proteins are highly sensitive to antigen, capable of inducing activation of host T cells at low concentrations of peptide antigen. In certain embodiments, binding proteins of the present disclosure are non-alloreactive against, are substantially non-alloreactive against, and/or have a low risk of alloreactivity against (i) amino acid sequences from the human proteome and/or (ii) against human HLA alleles. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented by a human leukocyte antigen (HLA) Class II molecule. 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) having antigenic specificity for an HLA-A11-restricted epitope of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) (KRAS.sub.7-16), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), or Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS). 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.