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 T cell receptors bind to a Ras antigen: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.

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.

The present invention relates to fusion proteins comprising a chimeric antigen receptor linked to a second polypeptide by a linker domain, wherein the second polypeptide prolongs the surface expression of the CAR, and wherein the linker is a cleavable linker. Also included are nucleic acids encoding the same, methods of treatments, and other methods or uses thereof.

The present application provides nucleated cells comprising a mutated Ras antigen (such as a mutated K-Ras antigen), methods of manufacturing such nucleated cells comprising the mutated Ras antigen, and methods of using such modified nucleated cells (e.g., immune cells) for stimulating an immune response, treating, and/or vaccinating an individual with a cancer associated with Ras mutation.

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.

The present disclosure relates to fusion proteins and methods of using them. The fusion protein may include an intracellular domain comprising an intracellular domain of an interleukin receptor polypeptide, or variant thereof that contributes to an interleukin signal in a host cell. The present disclosure also relates to uses of cells expressing such fusion proteins to treat certain diseases, such as cancer.

Contemplated cancer therapies comprise co-administration of aldoxorubicin with an immune therapeutic composition that preferably comprises a vaccine component and a cytotoxic cell component.

Embodiments of the disclosure include methods and compositions in which NK cells are modified by the hand of man to express T-cell receptor and CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with monospecific, bispecific or multi-specific antibodies, wherein the bispecific or multi-specific antibodies are tailored to comprise anti-CD3 antibodies that bind the modified NK cells, thereby triggering signaling, activation, and cytotoxicity of target cells to which the antibodies also bind. Thus, the NK cells are specifically configured to be able to work effectively with Bispecific NK cell engagers (BiKEs) as well as Bispecific T cell Engagers (BiTEs).

This invention relates to compositions and methods of treating cancer associated with mutant RAS. In certain aspects, the invention relates to antigenic RAS peptide fragments and T-cell receptors that bind to specific mutant RAS peptide fragments in the context of specific HLA types.