The present invention relates to a vector encoding a wildtype or truncated form of erythropoietin receptor (EpoR) to promote T cell survival and proliferation. Specifically, it exemplifies a bicistronic vector that expresses a truncated EpoR with an anti-CD19-41 BB-003 chimeric antigen receptor (CAR) that has a greater ex vivo expansion than CAR-T cells and demonstrates a significantly higher anti-leukemic activity in vivo. It also describes the method of producing cells expressing said vector and the use of these cells to kill CD19+ tumour cells.

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53.sup.R175H or human p53.sup.Y220C. 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 provides tumor neoantigenic peptide sequences and nucleotide sequences encoding such peptide sequences; a vaccine or immunogenic composition capable of raising a specific T-cell response comprising one or more of the neoantigenic peptides, or comprising nucleic acid encoding one or more of the neoantigenic peptides; an antibody, or an antigen-binding fragment thereof, a T cell receptor (TCR), or a chimeric antigen receptor (CAR) that specifically binds such neoantigenic peptides; methods of producing such antibodies, TCRs or CARs; polynucleotides encoding such neoantigenic peptides, antibodies, CARs or TCRs, optionally linked to a heterologous regulatory control sequence; immune cells that specifically bind to such neoantigenic peptides; and dendritic cells or antigen presenting cells that have been pulsed with one or more of the neoantigenic peptides; and methods of using such products in particular therapeutic uses of these products.

Systems and methods for predicting MHC presentation of a neoepitope of a tumor or for predicting an immune response against an MHC presented neoepitope of a tumor are disclosed. The methods use sequence information of the neoepitope.

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

The invention provides personal neoantigen vaccines, and uses thereof. The invention also provides markers MX1 and PPP1R15A, and uses thereof. The invention also provides sets of biomarkers, and uses thereof.

The invention provides a method for the expansion of anti-tumor T-cells, comprising the steps of: a) providing a phagocytosable particle, having one or more tumor neoantigenic constructs tightly associated thereto, wherein the tumor neoantigenic construct comprises an amino-acid sequence comprising at least one mutated amino acid known or suspected to be associated with a cancer in a subject, or a mutated or non-mutated amino-acid sequence known or suspected to be expressed in a cancer cell in the subject; b) providing a viable antigen-presenting cell; c) contacting the particle with the antigen-presenting cell in vitro under conditions allowing phagocytosis of the particle by the antigen-presenting cell; d) providing a T-cell sample comprising viable T-cells from the subject; e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle in vitro under conditions allowing specific activation of anti-tumor T-cells in response to antigen presented by the antigen-presenting cell.

The invention also provides tumor neoantigenic constructs as defined in the specification.

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

The disclosure relates to methods of manufacturing individualized vaccines that comprise nucleic acid molecules that encode one or more neoantigens specific for antigens that are expressed by a tumor in a subject. Compositions comprising coding regions encoding neoantigens organized in a pattern of nucleic acid sequences are also disclosed as well as methods of immunizing a subject using the same.

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.