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.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells.

Compositions and methods are provided for peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

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.

The present disclosure provides nucleic acid constructs for the treatment of cancer, comprising a cancer-specific promoter and one or more therapeutic genes.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.

Described herein are compositions and methods for signaling and antigen-presenting bifunctional receptors (SABRs) comprising one or more antigen presenting domains; and one or more signal transduction domains, wherein the one or more antigen presenting domains comprise a binding fragment of a major histocompatibility complex (MHC) molecule. Various immunological functions of the SABRs are also described.

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

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.

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