Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

The present application provides identification, in vitro amplification, and application method of memory CD8 T cells specific for an antigen in a solid tumor-draining lymph node.

The present invention relates to a targeting module comprising at least one CD123-binding domain and a tag-binding domain binding the human La epitope E5B9, a nucleic acid, a vector or a cell comprising a nucleotide sequence encoding the targeting module, a pharmaceutical composition and a kit comprising the targeting module and a vector or a cell comprising a nucleotide sequence encoding a reversible chimeric antigen receptor.

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.

The technology relates generally to the field of immunology and relates in part to compositions and methods for growing and storing modified natural killer cells, including for example, conditional chemical regulation of natural killer cell function. The technology further relates to pharmaceutical compositions and treatment of subjects using modified natural killer cells.

Provided herein are compositions and methods for genetically engineering a cell (e.g., a hematopoietic cell) to modify a gene encoding a lineage-specific cell-surface antigen to modify an epitope of the lineage-specific cell-surface antigen recognized by an agent. Also provided are methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy, as well as the genetically engineered cells themselves.

The present invention provides a composition comprising A) a nucleic acid sequence comprising encoding I) a) a fusion protein comprising from N-terminus to C-terminus i) IL-15R and, ii) the intracellular signaling domain of CD2, and b) IL-15, or II) a fusion protein comprising from N-terminus to C-terminus i) IL-15, ii) a linker, iii) IL-15Ra, and iv) the intracellular signaling domain of CD2, or B) a first nucleic acid sequence and a second nucleic acid sequence, said first nucleic acid sequence comprising encoding a fusion protein comprising from N-terminus to C-terminus i) IL-15Ra and ii) the intracellular signaling domain of CD2, said second nucleic acid sequence comprising encoding IL-15. Said composition may additionally comprise a transgene such as a CAR. Also disclosed are immune cells expressing the nucleic acids of said composition.

Chimeric antigen receptor molecules that include a variant IL-13. The variant IL-13 are more selective for IL13R2 than IL13R1 by virtue of weaker binding to IL13R1. The chimeric antigen receptors can be used to treat IL13R2 expressing cancers.

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 relates to a targeting module comprising at least one tumor-binding domain, in particular at least one IL13R2-binding domain and/or at least one HER2-binding domain, and a tag-binding domain or a tag for use in a method for stimulating a chimeric antigen receptor-mediated immune response in a mammal, a nucleic acid, a vector or a cell comprising a nucleotide sequence encoding the targeting module, a pharmaceutical composition and a kit comprising the targeting module and a vector or a cell comprising a nucleotide sequence encoding a switchable chimeric antigen receptor.