A combined artificial cell death/reporter system polypeptide containing a herpes simplex virus thymidine kinase (HSV-tk) fused to a prostate-specific membrane antigen (PSMA) polypeptide via a linker is described. Also described are polynucleotides encoding the artificial cell death polypeptide, cells expressing the artificial cell death polypeptide and related methods.

The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, shRNAs designed to downregulate CD52 are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy, especially in combination with immunosuppressive therapies directed against CD52, as is particularly envisaged in allogeneic therapy. The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. Further, strategies to treat diseases such as cancer using these cells are also provided. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are particularly suitable for treating lymphomas, multiple myeloma and leukemia.

Provided herein are methods for selecting a population of cells expressing a target polypeptide. In some aspects, the disclosure provides methods for sorting and selecting populations of transfected host cells based on their early expression of a selectable polypeptide. In certain embodiments, the sorting is performed using fluorescence-activated cell sorting or magnetic-activated cell sorting based on the selectable polypeptide. Such selection methods can be further utilized to generate clonal populations of producer cells, e.g. for large-scale manufacturing of a target polypeptide of interest.

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 to the use of a soluble CD52 glycoprotein in treating diseases regulated by effector T-cells, for example sepsis or multiple sclerosis. The present disclosure also relates to diagnostic methods based on the detection of CD52 expression levels in a subject.

The present disclosure provides nucleic acid molecules encoding an engineered antigen receptor, such as a chimeric antigen receptor or exogenous T cell receptor, and an inhibitory nucleic acid molecule, such as an RNA interference molecule. The present disclosure further relates to nucleic acids, DNA constructs, vectors, pharmaceutical compositions, genetically-modified cells, and methods of treatment that utilize the nucleic acid molecules of the invention.

Provided herein are recombinant glycoproteins (e.g., recombinant human α-galactosidase-A proteins) with an altered (e.g., improved) glycosylation profile, and pharmaceutical compositions and kits including one or more of these proteins. Also provided are methods of generating a mammalian cell useful for recombinant expression of a glycoprotein (e.g., recombinant human α-galactosidase-A), methods of producing recombinant glycoproteins, and methods of treatment that include administering to a subject at least one of the recombinant glycoproteins (e.g., recombinant human α-galactosidase-A protein).

The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, multiple shRNAs, designed to downregulate multiple targets are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy.

The present disclosure relates to glycoprotein CD52 and fusion proteins thereof, wherein the CD52 glycoprotein has α-2,3-sialylated N-glycans, O-glycosylation and a pI of about 5 to about 6. The disclosure further relates to the preparation and purification of these proteins and their use in the suppression of effector T-cell function and/or immune response, such as in the treatment of diseases or conditions mediated by effector T-cell function.

Provided herein are methods for pre-activating and expanding an isolated population of NK cells. Further provided herein are methods for the treatment of cancer by administering the pre-activated and expanded NK cells.