The present disclosure relates to genetically engineered hematopoietic cell/s, specifically, lymphocytes, and more specifically, cells of the T cell lineage or a cell population comprising at least one of the cell/s. The disclosed cells comprises and/or expresses at least one nucleic acid sequence encoding at least one molecule involved directly or indirectly in at least one metabolic pathway. The present disclosure provides compositions, methods and uses of the engineered cells.

Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.

This disclosure relates to modified receptors comprising a MyD88 domain, as well as cells comprising the same and methods of use thereof.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-targeted T cell receptors (TCRs) that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The present invention refers to an in vitro or ex vivo method for the treatment of isolated CD8+ T cells. In particular, it refers to an in vitro or ex vivo method for obtaining an isolated population of CD8+ T cells comprising exposing isolated CD8+ T cells to an excess of sodium chloride. CD8+ T cells obtained by such method, pharmaceutical compositions including them and their medical uses, in particular for the prevention and/or the treatment of cancer, are also within the invention.

Methods and compositions are provided for nuclease-mediated gene editing of primary cells without the use of viral mediated delivery. Methods of treatments using edited primary cells are also provided.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).