Modified macrophage immune cells are provided for treatment of cancer and other diseases.

According to the present invention, peptides having the amino acid sequence of SEQ ID NOs: 14, 21, 23, 27, 36, 46, 57, 60 and 62 were demonstrated to have cytotoxic T lymphocyte (CTL) inducibility. Therefore, the present invention provides a peptide having the amino acid sequence selected from among SEQ ID NOs: 14, 21, 23, 27, 36, 46, 57, 60 and 62. The peptide can include one, two, or several amino acid substitutions, deletions, insertions, or additions so long as its CTL inducibility is retained. Furthermore, the present invention provides pharmaceutical agents for the treatment and/or prophylaxis of cancers, and/or prevention of postoperative recurrence thereof, which contain any of these peptides. Pharmaceutical agents of this invention include vaccines.

Disclosed herein are methods of detecting a target viral nucleic acid sequence, determining the localization of the target viral nucleic acid sequence, and/or quantifying the number of target viral nucleic acid sequences in a cell. This method may be used on small target nucleic acid sequences, and may be referred to as Nano-FISH or viral Nano-FISH.

Neuroblastoma (NB) remains a leading cause of childhood cancer morbidity and mortality. Heritable activating mutations are present in the anaplastic lymphoma kinase (ALK) oncogene and these same mutations are frequently somatically acquired during high-risk NB tumorigenesis. ALK has been established as a tractable molecular target in NB and provides the rationale for the clinical development of ALK inhibition therapy. Anti-ALK antibodies and antigen binding fragments thereof are provided along with methods of use thereof.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as PTK7+ malignancies.

Provided herein are antibodies that specifically bind to Fms-like tyrosine kinase 3 (FLT3), chimeric antigen receptors (CARs) that specifically bind to FLT3, and engineered immune cells expressing such CARs (e.g. FLT3-specific CAR-T cells). The invention also provides making such antibodies, CARs, and engineered immune cells. The invention also provides using such antibodies, CARs, and engineered immune cells, for example for the treatment of a condition associated with malignant cells expressing FLT3 (e.g., cancer).

The present disclosure relates generally to compositions and methods for improving T cell therapy. In particular, the disclosure provides polypeptides and recombinant nucleic acid constructs and/or recombinant nucleic acids encoding polypeptides having mutations capable of altering T cell signaling, cytokine production, and/or in vivo persistence in tumors of therapeutic T cells comprising the mutation. The T cell signaling can be by NFAT, NF-B and/or AP-1 pathways. The disclosure also provides vectors and cells including the polypeptides and/or recombinant nucleic acid constructs and/or recombinant nucleic acids of the disclosure as well as methods of preparing a T cell for use in cell therapy, and methods of identifying a mutation useful for improving T cell therapy.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the cell-surface protein(s).

A population of genetically engineered T cells, comprising a disrupted Reg1 gene and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD70 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-b, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.