Provided herein are compositions and methods for manufacturing engineered lymphocytes. Also provided are the prepared engineered lymphocytes which have increased proportions of juvenile/naive lymphocytes leading to increased therapeutic efficacy. The methods in various embodiments are expedited as compared to the conventional technology, and produce lymphocytes with improved viability, transduction success rates, and in vivo antitumor efficacy.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

Disclosed herein are methods and compositions comprising placental adherent stromal cells for treating viral infections and sequelae thereof.

Provided is a method of transducing and expanding a population of cells, the method comprising, in order: a cell selection step; a pre-transduction activation step; a cell transduction step; and a cell expansion phase. At least the cell transduction step and the expansion phase comprise incubation of the cells with IL-15. The methods of the invention are well suited to the transduction and expansion of populations of cells expressing chimeric antigen receptors (CARs), and in particular for the transduction and expansion of populations of invariant natural killer T (iNKT) cells expressing CARs. Also provided are populations of cells produced by the methods of the invention, and pharmaceutical compositions comprising populations of cells, as well medical uses of the pharmaceutical compositions and populations of cells. The cells and pharmaceutical composition are suitable for application in medical use and methods of treatment, including immunotherapy.

The present disclosure relates to treating a subject comprising administering to the subject a therapy (e.g., a cell therapy, e.g., an adoptive cell therapy, e.g., a CAR-T cell therapy), wherein, prior to the administration, the subject has been preconditioned with a personalized amount of a chemotherapeutic agent. The personalized amount provides an optimal exposure to the chemotherapeutic agent.

The present invention relates to modified immune cells or precursors thereof, comprising dual (a first and a second) chimeric receptors (e.g. CARs). One aspect includes a first CAR comprising a 4-1BB intracellular domain and a second CAR comprising a CD28 intracellular domain. Another aspect includes a method for treating of an HIV infected mammal using a modified T cell comprising a first CD4 CAR comprising a 4-1BB intracellular domain and a second CD4 CAR comprising a CD28 intracellular domain.

Provided is a chimeric antigen receptor, comprising a ligand-binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain. The co-stimulatory domain comprises an intracellular region of an NK-activated receptor or a ligand thereof. Also provided are an engineered immune cell comprising the chimeric antigen receptor and a use thereof in treatment of diseases, such as cancers, autoimmune diseases, and infections.

Provided is an engineered immune cell. The engineered immune cell expresses (i) a chimeric receptor, and (ii) exogenous CCL3, CCL4 and/or CCL5, has improved tumor killing activity, and can be used to treat cancer, infection or autoimmune diseases.

T cells comprising a molecule comprising (i) a target-specific antigen-binding domain, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

The present invention provides a CD19-targeting humanized antibody, and a multispecific antibody, chimeric receptor, antibody conjugate, pharmaceutical composition, and kit comprising the CD19-targeting humanized antibody, and a use thereof in the diagnosis/treatment/prevention of diseases associated with CD19 expression.