Abstract:
There is provided herein a method for expanding human CD4-CD8- regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), preferably the DN Tregs are αβ-TCR-CD56- or alternatively γδ-TCR+.
Abstract:
A method of expanding double negative T cells in culture is described. The method comprises (a) providing a starting sample comprising DN T cells or precursors thereof; (b) substantially depleting CD8 + and CD4 + T cells from the starting sample; (c) culturing the sample from step (b) with an immobilized T cell mitogen in a culture medium comprising an agent that can stimulate DN T cell growth; (d) washing the cells obtained in step (c) and resuspending in a culture medium comprising the agent without the T cell mitogen; and (e) washing the cells obtained in step (d) and resuspending in a culture medium comprising the agent and a soluble T cell mitogen. The DN T cells obtained by the method are useful in a variety of applications including the treatment of cancer, infectious diseases, graft versus host disease and autoimmune disease.
Abstract:
The disclosure relates to the development and use of CD4- CD8- double negative T (DNT) cells genetically modified to bind to one or more target antigens to enhance DNT cell anti-cancer activity such as with a chimeric antigen receptor (CAR). Genetically modified DNT cells can be generated ex vivo and expanded from allogeneic healthy donor cells and used as off-the-shelf therapy to overcome allogeneic graft-versus-host disease (GvHD) and/or host-versus-graft rejection in the treatment of cancer.
Abstract:
Methods of treating T cells with Venetoclax to increase T cell-mediated cytotoxicity and/or T cell mediated anti-tumor activity are described. Also described are populations of enhanced T cells as well as associated methods and uses for the treatment of cancer.
Abstract:
Described are methods for the production and use of cryopreservable double negative T cells (DNTs) for the treatment of cancer as an off-the-shelf cellular therapy. A sample population of DNTs is expanded using DNTs from one or more donors. The expanded population of DNTs from different donors does not exhibit alloreactivity against allogenic cells in the expanded population. The expanded populations of DNTs can be long-term stored as cryopreserved products.
Abstract:
Methods for the treatment of cancer using double negative (DN) T cells are described. The DNTs may be used for the treatment of chemotherapy- resistant cancers such as recurring or relapsing acute myeloid leukemia (AML). The use of allogenic DNTs, such as those derived from healthy donors, that do not exhibit toxicity towards normal host tissues and the complications associated with graft-versus-host-disease, is also described.
Abstract:
The present application provides a novel antibody that is specific for MFAP4. The application also provides methods and uses of MFAP4 as a marker for regulatory cells and/or anti-cancer cells. Further, the application provides methods and uses of MFAP4 binding agents for selection and activation of regulatory cells and/or anti-cancer cells.
Abstract:
Methods for the treatment of cancer using double negative (DN) T cells are described. The DNTs may be used for the treatment of chemotherapy-resistant cancers such as recurring or relapsing acute myeloid leukemia (AML). The use of allogenic DNTs, such as those derived from healthy donors, that do not exhibit toxicity towards normal host tissues and the complications associated with graft-versus-host-disease, is also described.
Abstract:
A method of expanding double negative T cells in culture is described. The method comprises (a) providing a starting sample comprising DN T cells or precursors thereof; (b) substantially depleting CD8+ and CD4+ T cells from the starting sample; (c) culturing the sample from step (b) with an immobilized T cell mitogen in a culture medium comprising an agent that can stimulate DN T cell growth; (d) washing the cells obtained in step (c) and resuspending in a culture medium comprising the agent without the T cell mitogen; and (e) washing the cells obtained in step (d) and resuspending in a culture medium comprising the agent and a soluble T cell mitogen. The DN T cells obtained by the method are useful in a variety of applications including the treatment of cancer, infectious diseases, graft versus host disease and autoimmune disease.