The inventive subject matter relates to methods for treating a T-cell deficiency in a subject in need thereof, comprising administering to said subject a T-cell precursor isolated from an allogeneic donor, provided that said allogeneic donor is not MHC-matched to said subject. The inventive methods can be further enhanced by genetic engineering for targeted immunotherapy.

Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

Disclosed herein are methods for generating universal MHC/HLA-compatible hematopoietic progenitor cells and methods for generating custom patient-specific MHC/HLA-compatible hematopoietic progenitor cells. Compositions comprising the universal and custom hematopoietic progenitor cells and therapeutic applications thereof are also disclosed.

This disclosure provides miRNA/mRNA pairs that can be used to increase the efficacy of T cells or to down-modulate T cell efficacy and restore equilibrium.

Provided herein are innate immune cells for use in therapeutic methods. Also described herein are pharmaceutical compositions comprising innate immune cells for use in the treatment of a variety of diseases including, but not limited to pathogenic infections, pulmonary diseases, inflammatory diseases, autoimmune diseases, and immunodeficiency.

Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

The present disclosure relates to expansion and activation of T cells. In an aspect, the present disclosure relates to expansion and activation of ?? T cells that may be used for transgene expression. In another aspect, the disclosure relates to expansion and activation of ?? T cells while depleting ?- and/or ?-TCR positive cells. T cell populations comprising expanded ?? T cell and depleted or reduced ?- and/or ?-TCR positive cells are also provided for by the instant disclosure. The disclosure further provides for methods of using the disclosed T cell populations.

Methods of treating a subject with a tumor, for example in combination with cancer immunotherapy are provided. In some embodiments, the methods include obtaining one or more samples including tumor cells from the subject and measuring human leukocyte antigen (HLA) and/or 2-microglobulin (B2M) expression level, genotype, and/or copy number in the tumor cells. One or more HLA and/or B2M alleles with reduced expression, function, and/or copy number in the tumor are selected and a nucleic acid encoding the one or more HLA and/or B2M alleles is administered to the subject. One or more cancer immunotherapies are also administered to the subject.

Provided are methods, compositions, uses and articles of manufacture of combination therapies involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and the use of (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, for treating subjects with disease and conditions such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the disease or condition is a non-Hodgkin lymphoma (NHL), such as relapsed or refractory NHL or specific NHL subtype.

The invention provides methods of depleting CD5+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD5 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.