The present disclosure concerns dosages for the treatment of human patients susceptible to or diagnosed with a disease, such as cancer. Provided are methods for administering chimeric antigen receptor (CAR)-T cells. Also provided are compositions and articles of manufacture for use in the methods.

Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes an antigen. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

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.

This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

Anti-CD19 antibodies (e.g., UniAbs?) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of CD19.

Provided herein are targeted cytokine constructs and method of engineered cell therapy by administering a targeted cytokine construct in combination with an engineered cell therapy, for use in treating a disease, e.g., a proliferative disease, e.g., a cancer.

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 are chimeric antigen receptors (CARs), which contain extracellular antigen-binding domains that bind to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and B-cell maturation antigen (BCMA). The disclosure further relates to genetically engineered cells expressing such CARs, and uses thereof in adoptive cell therapy.

Methods of producing T cells having reduced surface fucosylation and use thereof in adoptive cell therapy, in particular, in cancer treatment are provided.

The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) off-the-shelf T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.