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 family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0?10.sup.6 CAR123 T cells results in significantly delayed leukemic progression in mice. These results suggest that CD123CAR-transduced T cells may be used as an immunotherapy for the treatment of high risk AML.

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.

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.

Antigen binding molecules capable of binding to CDI22 and/or common y chain (CDI32) are disclosed herein. Also disclosed are compositions comprising such antigen binding molecules, and uses and methods using the same.

Provided herein are, inter alia, methods, compositions and kits for treating cancer, e.g., acute myeloid leukemia, including an engineered cell including various CAR constructs. Also included herein are kits for treating cancer, including engineered cells comprising various CAR constructs.

Provided is an antibody that specifically recognizes IL-13RA2, which can be used in the manufacture of a targeting anti-tumor medicament as well as a medicament for diagnosing a tumor.

Described herein are methods of promoting engraftment of a cell transplant and methods of killing hematopoietic stem cells by administering a population of T cells, NK cells or cytotoxic immune effector cells comprising a cell-surface receptor for a stem cell-specific antigen. Also described herein is a composition comprising T cells, NK cells or cytotoxic immune effector cells genetically modified to encode a cell-surface receptor for a stem cell-specific antigen.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The invention relates to cell death inducing chimeric antigen receptors (D-CAR). In particular, the present invention relates to cell death inducing chimeric antigen receptors which comprise at least one death domain in their endodomain, including cell death inducing chimeric antigen receptors comprising within their death domains modifications which attenuate the self-association and/or binding to pro-apoptotic or pro-necrotic adaptor proteins, such as FADD or TRADD. Moreover, the present invention relates to an engineered immune cell expressing at its surface a cell death inducing CAR of the present invention and, optionally, an activating chimeric antigen receptor, wherein the extracellular ligand-binding domains of the cell death inducing CAR and the activating CAR bind to different antigens. The engineered immune cell may furthermore comprise at least one edited (e.g., inactivated) gene selected from TCR genes, immune check point genes, genes involved in drug resistance, and combinations thereof.