The present invention relates to engineering synthetic MHC molecules with novel peptide binding properties, by exploring combinations of groove specificities from naturally occurring MHC-I alleles using structure-guided modeling and design. The invention also relates to generating a chimera, each involving computer implementation, storage of data on a memory device, and the data including data set(s) for making comparisons and accepting or rejecting structures, and with each involving synthesis and expression, including as herein further discussed:

Provided herein are cells or populations of cells comprising a polynucleotide encoding a cleavage resistant CD16 polypeptide. Also provided herein are methods of suppressing the proliferation of tumor cells such as HER2+ and methods of treating cancers, such as HER2+ in a subject with populations of placental-derived natural killer cells or placental-derived T cells comprising a cleavage resistant CD16. The natural killer cells, such as CYNK cells, can be placental CD34+ cell-derived natural killer (NK) cells. The placental-derived T cells can be isolated from cord blood or from placental perfusate.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

The present invention is generally directed to a colorectal (CRC) cell atlas that provides methods of predicting outcomes of cancer patients and therapeutic targets for treating patients in need thereof. The atlas may be used to predict a response to immunotherapy, in particular checkpoint blockade therapy and adoptive cell transfer. Disclosed herein are previously unidentified gene programs in tumors that can be used to predict response and provide for therapeutic targets that can be used to shift a tumor to a responsive phenotype.

The present disclosure relates to the fields of molecular biology, more specifically antigen-binding molecule technology. The present disclosure also relates to methods of medical treatment and prophylaxis, particularly cellular immunotherapy.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

Provided herein are methods of producing a composition comprising genetically engineered cells for cell therapy, the method comprising: selecting one or more genetically engineered cells from a population of cells, and formulating the composition comprising the selected one or more genetically engineered cells for use, wherein the one or more genetically engineered cells comprise one or more genetic modifications, and wherein the one or more genetically engineered cells are selected based on a level of one or more markers on the cell surface of the one or more genetically engineered cells, as well as compositions derived therefrom.

Disclosed herein are recombinant nucleic acids, comprising a 5 untranslated (5-UTR) sequence portion, a signal peptide sequence portion, a single chain antibody fragment sequence portion, a hinge region sequence portion, a transmembrane domain sequence portion, and one or more intracellular domain sequence portions. Also disclosed herein are modified natural killer (NK) cells comprising the recombinant nucleic acid described above. Further disclosed herein are methods of treating a tumor in a subject by administering the modified NK cells.

The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.