The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and/or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

Aspects of the present disclosure include improvements to chimeric antigen receptor (CAR) constructs, CAR comprising immune cells, as well as methods for making such constructs and/or cells and methods for their use in treatment of disease (e.g., cancer). Disclosed are immune cells comprising CARs comprising CD30-derived hinge and/or transmembrane and methods for use of such cells in treatment of malignancies (e.g., B-cell malignancies). Also disclosed are polynucleotides encoding a CAR comprising CD30-derived hinge and/or transmembrane domains, as well as cells comprising such polynucleotides and pharmaceutical compositions comprising such cell

The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor antigens. It relates to cells comprising a first antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) and a second antigen-recognizing receptor (e.g., a TCR-like fusion molecule). These cells have improved activity and/or efficiency.

The disclosure is directed to methods and compositions for treating cancers characterized by cells comprising chimeric antigen receptors (CARs) that bind CD70 and T-cell engaging antibody molecules (TEAMs) that bind CD33, nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind CD70 and/or TEAMs that bind CD33, and compositions and methods related thereto.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

The present invention relates to an anti-CD70 nanoantibody and a use thereof. The present invention provides a CD70 binding molecule, containing the anti-CD70 nanoantibody or an antigen binding fragment thereof. Complementarity-determining regions (CDRs) of the anti-CD70 nanoantibody comprise CDR1, CDR2 and CDR3. The present invention also provides a chimeric antigen receptors containing the CD70 binding molecule and an expression cell thereof. The antibody and the cell of the present disclosure have good safety and therapeutic effects targeting CD70.

A gene using a BCMA extracellular domain as a marker, a polypeptide, a recombinant expression vector, a genetically engineered cell, and use thereof are provided. The gene tBCMA is a gene encoding a complete or partial sequence of the BCMA extracellular domain, or a gene encoding a sequence at least 85% identical to the complete or partial sequence. An extracellular domain polypeptide (tBCMA) of the B cell maturation antigen is used as a marker for the technology of detecting and removing the genetically engineered immune cells. The gene using the BCMA extracellular domain as the marker can be widely used for the detection of various genetically engineered immune cells, thereby effectively solving the problems of detection of the genetically engineered immune cells after preparation and infusion, and providing a feasible strategy when these cells need to be removed due to serious toxic and side effects in clinical therapy.

Embodiments of the disclosure encompass methods and compositions that utilize an anti-CD70 chimeric antigen receptor (CAR) that lacks an antibody or antibody fragment as part of the receptor, including as part of the antigen binding region of the CAR. In particular embodiments, instead of the CAR employing an antibody to bind CD70, the CAR molecule utilizes CD27, the receptor for the ligand CD70. In specific embodiments, the CAR comprises a truncated version of CD27 rather than full length CD27. In specific cases, the CAR lacks the CD27 transmembrane domain.

Disclosed herein are polynucleotides and vectors encoding improved immunotherapeutics, polypeptides encoded by the polynucleotides and/or vectors, cells expressing the polypeptides, and pharmaceutical compositions comprising the polynucleotides, vectors, polypeptides, and/or cells.