Disclosed provides a method of treating measure residue disease (MRD) in a subject with cancer using an allogeneic leukemia-derived cell as a vaccine based on the information provided by prognostic biomarkers comprising dendritic cells including cDC1 cDC2, and/or pDC; CD8+ T cells including CD8+CD45RA+ cells, CD8+CD45RA? CCR7+CM T cells, and/or CD8 RO+ T cells; B cells; NK cells including CD56++NK cells and/or CD56+NK cells; CD4 CD161+ T cells; CD14+CD16? non-inflammatory monocytes, or any combination thereof.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

A cell for immunotherapy of the present invention includes a nucleic acid encoding a Wilms tumor 1 gene product or a fragment of the Wilms tumor 1 gene product, wherein the nucleic acid including (i) a region encoding a fragment of the Wilms tumor 1 gene product, the fragment being indicated by positions 194 to 493 of amino acid sequence of SEQ ID NO:1 or by positions corresponding to the positions 194 to 493 of amino acid sequence corresponding to SEQ ID NO:1 and (ii) only one AUG as a functional start codon, connected to a 5 terminal side of the region via 3m (m is 124-192) bases intervening between the AUG as the functional start codon and the 5 terminal side of the region, and a nucleic acid encoding CD1d, wherein the cell has been loaded with a glycolipid recognized by antigen receptor of NKT cell.

Provided is a method for inducing CD4.sup.?CD8.sup.+ T cells having an antigen specific cytotoxic activity from pluripotent stem cells, comprising the steps of: (1) differentiating pluripotent stem cells to give a cell culture comprising CD4.sup.?CD8.sup.? T cells and CD4.sup.+CD8.sup.+ T cells, (2) removing CD4.sup.?CD8.sup.? cells from the cell culture obtained in step (1), and (3) differentiating the CD4.sup.+CD8.sup.+ cells in the cell culture into CD4.sup.?CD8.sup.+ T cells.

Described herein are immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. Some immunomodulatory fusion proteins as described comprise a SIRP? extracellular component and hydrophobic and intracellular components comprising transmembrane and/or signaling domains of a CD28, respectively. Such fusion proteins are capable of delivering a positive or costimulatory signal in response to a binding event that in a natural setting would result in an inhibitory signal. Uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease, are also described.

The present invention pertains to polynucleotides that encode CDR3 in TCR-[alpha] and TCR-[beta] chain genes of CD4.sup.+ helper T-cells that are specific to WT1 helper peptides having an amino acid sequence represented by SEQ ID NO: 123. The present invention further pertains to the peptides encoded by said polynucleotides. The present invention further pertains to CD4.sup.+ T cells into which TCR genes that contain said polynucleotides have been introduced, the induction of WT1-specific cytotoxic T-lymphocytes (CTLs) using the CD4.sup.+ T-cells, the treatment of cancer, etc.

The present invention provides an isolated cell composition suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 10.sup.6 CD8+ T cells specific for target peptide antigen(s). In various embodiments, the composition is predominately CD8+ T cells, and at least about 20% of T cells in the composition exhibit a central or effector memory phenotype, providing for a robust and durable adoptive therapy from a natural T cell repertoire that has undergone natural selection.

[Problem] To provide a polypeptide which enables stimulation of numerous T cells of different derivation, and to induce strong immunological response against numerous types of cancers. [Solution] Provided is a fused polypeptide that includes a helper epitope derived from the WT1 protein, and a killer epitope derived from the WT1 protein, wherein the polypeptide includes a total of 3 to 6 of the helper epitopes and the killer epitopes per molecule of the fused polypeptide.

This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT-1-expressing cancer, comprising peptides derived from the WT-1 protein.

The present invention is directed to a nucleic acid molecule comprising a polynucleotide sequence encoding a chimeric antigen receptor comprising (a) an anti-CLEC14A binding domain, (b) a transmembrane domain and (c) an intracellular signalling domain; wherein said anti-CLEC14A binding domain is capable of binding to the C-type lectin domain of CLEC14A. The invention further provides a chimeric antigen receptor encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a cell comprising the nucleic acid molecule, vector or CAR and the therapeutic use of the nucleic acid, vector or cell, particularly in treating CLEC14A expressing conditions.