Abstract: 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.

Abstract: Methods of cane r treatment based, on personalized vaccines are disclosed. Individual amino acid substitutions from tumors are revealed using whole genome sequencing, and identified as neoantigens silico. Peptide sequences are then tested in vitro for ability to bind HLA molecules and to be presented to CD8+ T-cells. A vaccine is formed using neoantigen peptides and an adjuvant or dendritic cells (DC) autologous to a subject. In the latter, autologous DC are matured and contacted with the neoantigen peptides. The DC are then administered to the subject. PBMC are then obtained from the subject, and CD8+ T cells specific to the neoantigens are cultured and enriched. Enriched T-cells are then administered to the subject to treat cancer. Treatment resulted in tumor regression in mice bearing human melanomas, and complete or partial responses were observed in human patients.

Abstract: Single chain trimer (SCT) molecules are disclosed, comprising an MHC antigen peptide sequence, a ?2-microglobulin sequence and a full-length MHC class I heavy chain sequence, joined by linker sequences. Further described are nucleic acids encoding single chain trimers. Methods for expansion of antigen-specific T cell populations using single chain trimer molecules are also disclosed. In some configurations, these methods comprise co-culturing, in a first stage, CD8+ T cells from a donor with antigen presenting cells comprising an MHC antigen peptide, and co-culturing, in a second stage, the CD8+ T cells with cells comprising an SCT which has an MHC antigen peptide sequence identical to the sequence of the antigen peptide in the first stage. The methods can provide 10,000-100,000 fold expansion of antigen-specific CD8+ T cells within about 28 days after establishing culture, and can yield over 1 billion antigen-specific CD8+ T cells expanded from an individual donor.

Abstract: Single chain trimer (SCT) molecules are disclosed, comprising an MHC antigen peptide sequence, a ?2-microglobulin sequence and a full-length MHC class I heavy chain sequence, joined by linker sequences. Further described are nucleic acids encoding single chain trimers. Methods for expansion of antigen-specific T cell populations using single chain trimer molecules are also disclosed. In some configurations, these methods comprise co-culturing, in a first stage, CD8+ T cells from a donor with antigen presenting cells comprising an MHC antigen peptide, and co-culturing, in a second stage, the CD8+ T cells with cells comprising an SCT which has an MHC antigen peptide sequence identical to the sequence of the antigen peptide in the first stage. The methods can provide 10,000-100,000 fold expansion of antigen-specific CD8+ T cells within about 28 days after establishing culture, and can yield over 1 billion antigen-specific CD8+ T cells expanded from an individual donor.