The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.

Chimeric antigen receptors containing TSLPR-CD19 and TSLPR-CD22 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in an endogenous gene locus encoding DNMT3A. Compositions and methods of treatment are also provided.

Disclosed is an sgRNA guiding a PD1 gene for cleavage to achieve the efficient integration of exogenous sequences. The method for gene editing a PD1 gene in cells includes the steps of introducing a nuclease and an sgRNA into cells, and gene-editing the PD1 gene. The sgRNA guides the nuclease to cleave the PD1 gene and forms a broken site, at which an exogenous donor repair template can also be introduced, so that CAR-T elements can be directionally inserted at the specific site of the PD1 locus to construct enhanced CD19-CART cells with PD1 knockout in one step.

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

The invention provides novel peptides (e.g., linkers) and polypeptide compositions comprising the linkers (e.g., fusion proteins) and methods of using the polypeptide compositions. Peptides (e.g., linkers) are useful as tags and for engineering fusion proteins (e.g., antigen binding molecules, scFv). Polypeptide linkers described herein facilitate flexibility of linked peptides allowing for proper folding, conformation and reduced immunogenicity.

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 co-stimulatory 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.

The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.

A chimeric antigen receptor (CAR) cell library is established through the fusion of a cell and a vector assembly. The vector assembly carries three genetic elements corresponding to a plurality of first genetic elements encoding one or more idiotype CARs, a second genetic element carrying one or more genetic circuits, and a third genetic element encoding one or more inducible proteins, respectively. The one or more genetic circuits are pre-programmed and are each a combination of a cis-regulatory factor and a transcription factor; and the one or more inducible proteins include one or two selected from the group consisting of a drug resistance protein and a suicide protein. By designing a CAR library-genetic circuit-inducible protein coupling scheme, the cell library construction and screening for complex and unknown disease target antigens are realized, such as to solve the problems that there are complex, diverse, and variable antigens.

The present invention provides biocircuit systems, effector modules and compositions for cancer immunotherapy. Methods for inducing anti-cancer immune responses in a subject are also provided.