Abstract: The present invention relates to a method of generating ?? T cells having at least one down-regulated co-inhibitory receptor, the method comprising the steps of: (a) culturing a population of cells comprising ?? T cells with a phosphoantigen to expand the ?? T cells; and (b) culturing the expanded ?? T cells with artificial antigen-presenting cells expressing a Fc receptor, and an anti-CD3 antibody. The present invention also relates to ?? T cells generated according to a method of the present invention, as well as methods of treatment and medical uses thereof.

Abstract: The present invention relates to a method of generating ?? T cells having at least one down-regulated co-inhibitory receptor, the method comprising the steps of: (a) culturing a population of cells comprising ?? T cells with a phosphoantigen to expand the ?? T cells; and (b) culturing the expanded ?? T cells with artificial antigen-presenting cells expressing a Fc receptor, and an anti-CD3 antibody. The present invention also relates to ?? T cells generated according to a method of the present invention, as well as methods of treatment and medical uses thereof.

Abstract: Human pluripotent stem cells (hPSCs), especially induced pluripotent stem cells (iPSCs) provide a promising starting material to produce mimetic innate immune cells such as natural killer (NK) cells and ?? T-cells for cancer immunotherapy. To facilitate consistent mass production, an overall manufacturing scheme to make mimetic innate immune cells from hPSCs was designed and demonstrated. Particularly, a robust protocol to differentiate hPSCs into NK cells or ?? T-cells through sequential hematopoietic differentiation on stromal cell line deficient in expressing M-CSF and lymphoid commitment on stromal cell line deficient in expressing M-CSF ectopically expressing DLL1 without employing CD34+ cell enrichment and spin embryoid body formation is established. Using this two-stage protocol, the generation of functional mimetic NK cells and functional mimetic ?? NKT-cells was demonstrated from hPSCs, including hESCs, peripheral blood cell-derived iPSCs (PBC-iPSCs).

Abstract: There is provided a method of loading antigen in a dendritic cell for antigen presentation, the method comprising: modifying a pluripotent stem cell with a nucleic acid molecule encoding an antigen or one or more immunogenic epitopes thereof; inducing the pluripotent stem cell to differentiate into a dendritic cell that expresses and presents the antigen or the one or more immunogenic epitopes thereof. Dendritic cells, vaccines and methods of using the dendritic cells and vaccines are also provided.

Abstract: The invention concerns a method of preparing a composition comprising stimulated immune system cells such as dendritic cells (DC) for use in inducing immune response of cytotoxic T lymphocytes against colorectal cancer. The dendritic cells are pulsed by contact with colorectal cancer stem cells (CSC) or their fragments thereof. These colorectal CSCs are produced by OSKM (Oct4, Sox2, Klf4 and c-Myc) induced reprogramming of differentiated colorectal cancer cells (CRC) which results in undifferentiated colorectal CSC-like cells. Both the CSC-like cells and the lysates of heat-shocked CSC-like cells could be used as an accessible source of tumour antigens for DC pulsing to induce specific immune responses against colorectal CSCs.

Abstract: The manipulation of human dendritic cells (DCs) to induce potent anti-tumor immunity remains an essential subject of study. Here we report that the overexpression of CD1d in human DCs can enhance the priming of naïve CD8+ T cells against tumor antigen. We showed that CD1d can be overexpressed in the human DCs using baculoviral vector carrying the CD1d gene. This CD1d-overexpression is functional as demonstrated by the increased expansion of invariant natural killer T (iNKT) cells while using these modified DCs to present ?-galactosylceramide (?-GC). Pulsed with tumor antigenic peptide, these CD1d-overexpressing human DCs showed enhanced capability to prime naïve CD8+ T cells. CD1d-overexpressing human DCs also induced a pro-inflammatory cytokine profile that may favor the priming. Moreover, this CD1d-overexpression strategy can be extrapolated to monocyte-derived human DCs.

Abstract: There is provided a method of delivering a nucleic acid molecule to an embryonic stem cell, including a human embryonic stem cell, by infecting the embryonic stem cell with a baculoviral vector comprising the nucleic acid molecule. Embryonic stem cells transduced by this method are useful for treating a disease or disorder in a subject.

Abstract: The invention provides a novel recombinant polypeptide that comprises a nucleic acid binding element and a hairpin motif that selectively binds to a neurotrophin receptor. The recombinant polypeptide may be used for neurotrophin receptor mediated delivery of nucleic acid, including therapeutic DNA, bound to the recombinant polypeptide. In one embodiment, the hairpin motif is a hairpin motif of a neurotrophin, such as nerve growth factor, brain derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. The hairpin motif is also a neurotrophin agonist and therefore may be used to treat any disorder responsive to neurotrophin treatment, such as neurological disorders and tumour. In one embodiment the agonist comprises a hairpin motif that selectively binds to a neurotrophin receptor and a positively charged binding domain which is believed to enhance receptor binding by binding to negatively charged cell membrane.

Abstract: The invention provides a novel recombinant polypeptide that comprises a nucleic acid binding element and a hairpin motif that selectively binds to a neurotrophin receptor. The recombinant polypeptide may be used for neurotrophin receptor mediated delivery of nucleic acid, including therapeutic DNA, bound to the recombinant polypeptide. In one embodiment, the hairpin motif is a hairpin motif of a neurotrophin, such as nerve growth factor, brain derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. The hairpin motif is also a neurotrophin agonist and therefore may be used to treat any disorder responsive to neurotrophin treatment, such as neurological disorders and tumour. In one embodiment the agonist comprises a hairpin motif that selectively binds to a neurotrophin receptor and a positively charged binding domain which is believed to enhance receptor binding by binding to negatively charged cell membrane.