The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising chimeric antigen receptors (CARs) specific for CD45. In certain embodiments, the modified immune cells or precursors thereof further comprise or instead comprise a modified endogenous gene locus encoding CD45.

The present disclosure provides gene editing methods for modulating the expression of an inhibitor of DNA-binding E-protein transcription factors, namely Id3, and thereby affecting T cell function. First, it provides experimental evidence that Id3 is critical to the persistence and function of tissue-infiltrating GVHD T cells in a mouse model. Id3 reduces chromatin accessibility (ChrAcc) of transcription factors (TFs) that drive T cell PD-1 transcription, differentiation and dysfunction. Id3 loss increases PD-1 expression and impairs tissue-infiltrating Th1 cells. Second, it provides proof-of-concept that targeting ID3 in human T cells using a CRIPSR/Cas9 knockout (KO) prevents xeno-GVHD but preserves the anti-leukemic activity of chimeric antigen receptor (CAR)-T cells. Third, it provides experimental evidence that ectopic expression of Id3 in engineered human CAR-T cells enhances the ability of these cells to eliminate tumors.

Embodiments of the present disclosure include methods and compositions related to CD105-targeting polypeptides. In some aspects, disclosed are chimeric receptors engineered to bind to CD105. Cells (e.g., NK cells, T-cells) expressing CD105-targeting peptides are described. Also described are therapeutic methods using polypeptides of the disclosure.

The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

An antigen-binding domain, antibody or chimeric antigen receptor that binds to CD84.

The present disclosure relates to anti-glyco-LAMP1 antibodies and antigen binding fragments thereof that specifically bind to a cancer-specific glycosylation variant of LAMP1 and related fusion proteins and antibody-drug conjugates, as well as nucleic acids encoding such biomolecules. The present disclosure further relates to use of the antibodies, antigen-binding fragments, fusion proteins, antibody-drug conjugates and nucleic acids for cancer therapy.

Provided are polynucleotides encoding inactivated cell surface receptors. Also provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

The present invention provides an anti-B7-H3 monoclonal antibody and use thereof in cell therapy. Specifically, the present invention provides an scFv, an antibody, and a specific CAR-T cell specifically targeting B7-H3. The present invention further provides an engineered immune cell capable of co-expressing a CAR targeting B7-H3 and a chimeric molecule or a secreted protein of PD-L1, the engineered immune cell having good tumor killing effects.