Provided herein are, inter alia, compositions comprising ex vivo expanded ILC1 cells, methods of preparing the compositions, and methods useful for treating cancer and leukemia.

A CD7-targeted engineered immune cell, a chimeric antigen receptor, a CD7 blocking molecule and the use thereof. A natural ligand of human CD7 is used for substituting for an antibody sequence to serve as an antigen recognition domain of a CD7-specific CAR-T or CAR-NK cell. The advantage of using human CD7 as the antigen recognition domain in the CD7-specific CAR is that cellular and humoral reactions produced by a host can be prevented, to achieve long-term durability and better efficacy of the CAR-T cell.

The present invention relates to a modified T cell, comprising (a) a disrupted endogenous CD28-encoding gene; and (b) a polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises in its ectodomain at least one antigen binding moiety that is capable of specific binding to the extracellular portion of CD28. The invention furthermore relates to a population of the modified T cells, to a method for generating modified T cells and medical and non-medical uses thereof.

The present invention relates to compositions and methods of generating modified hematopoietic stem or progenitor cells. One aspect of the invention includes a modified hematopoietic stem or progenitor cell comprising a nucleic acid capable of decreasing expression of an endogenous gene or a portion thereof, wherein the endogenous gene encodes a polypeptide comprising an antigen domain targeted by a chimeric antigen receptor (CAR). Another aspect of the invention includes a method for generating a modified hematopoietic stem or progenitor cell. Also included are methods and pharmaceutical compositions comprising the modified cell for adoptive therapy and treating a condition, such as an autoimmune disease or cancer.

This disclosure relates to chimeric antigen receptors targeting T cell malignancies. The present disclosure also relates to the development of methods for inactivation with engineered CARs, to enhance T cell functions or reduce T cell suppression.

Provided are an anti-B7H3 chimeric antigen receptor and an application thereof. The anti-B7H3 chimeric antigen receptor comprises an antigen binding domain, a hinge region, a transmembrane domain and a signaling transfer structural domain. The antigen binding domain is an anti-human B7H3 antibody. The anti-B7H3 chimeric antigen receptor has a specific targeting effect on B7H3-positive tumor cells, T cells that express the anti-B7H3 chimeric antigen receptor have significant killing effects in vitro and in vivo, can effectively remove the B7H3-positive tumor cells, and having important significance in the field of tumor therapy.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first costimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g. PD-1 or TIM-3) is downregulated.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen, e.g., CD33 or EMR2, and a population of hematopoietic cells that are altered in the expression of the lineage-specific cell-surface antigen, e.g., CD33 or EMR2, for immunotherapy of hematological malignancies. Also disclosed herein are methods of administering an agent targeting more than one lineage-specific cell-surface antigen, and a population of hematopoietic cells that are altered in the expression of more than one lineage-specific cell-surface antigen, for immunotherapy of hematological malignancies. Cells comprising mutations in CD33, or EMR2, or more than one lineage-specific cell-surface antigen are also provided, as are methods of producing such cells using CRISPR-based base editor systems.