Agency for Science, Technology and Research

Jieming Zeng

Shu Wang

Shan Shan Wu

Wei Xia Ang

Nan Ma

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 γδ 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 γδ 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 γδ NKT-cells was demonstrated from hPSCs, including hESCs, peripheral blood cell-derived iPSCs (PBC-iPSCs). non-T cell-derived iPSCs or γδ T cell-derived iPSCs and the use of these mimetic innate immune cells in killing cancer cells.

Methods for generating mimetic innate immune cells from pluripotent stem cells

The present invention relates to a method of generating &#x3b3;&#x3b4; T cells having at least one down-regulated co-inhibitory receptor, the method comprising the steps of: (a) culturing a population of cells comprising &#x3b3;&#x3b4; T cells with a phosphoantigen to expand the &#x3b3;&#x3b4; T cells; and (b) culturing the expanded &#x3b3;&#x3b4; T cells with artificial antigen-presenting cells expressing a Fc receptor, and an anti-CD3 antibody. The present invention also relates to &#x3b3;&#x3b4; T cells generated according to a method of the present invention, as well as methods of treatment and medical uses thereof.

Gamma delta T cells and a method of augmenting the tumoricidal activity of the same

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.

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Singapore, Singapore

Jieming Zeng