Provided herein are compositions of NK-92 cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

Described herein are chimeric proteins including membrane-cleavable chimeric proteins and degron-fusion chimeric proteins. Also described herein are nucleic acids, pharmaceutical compositions, methods, and methods of treatment directed to the same.

The present invention relates to modified T cells, and in particular to CD8 T cells, for use in therapy. The current inventors investigates the effect of CXCR4.sup.Whim mutation on CD8 effector and memory responses. By analysing the lymphoid organs, including the BM compartment, in a mouse model of Whim syndrome and in mice where only CD8 T-cells carry the mutation, this study shows that CXCR4.sup.Whim mutation only partially affect CD8 primary responses. By contrast, CXCR4.sup.Whim mutation considerably improve the long-term maintenance and magnitude of CD8 memory responses by increasing the pool size of Antigen specific CD8 T-cells, first in the BM and then in other lymphoid organs, bringing new insight into the current discrepancy regarding the role of the BM in the maintenance CD8 memory cells. In particular, the present invention relates to T cell, and more particular to CD8 T cell, characterized in that it expresses CXCR4.sup.Whim mutation or a CXCR4 with the deletion of the C-terminal domain between and 20 amino acid residues.

This disclosure relates to therapeutics containing IL-37, chimeric antigen receptors, nucleic acids, or vectors encoding the same. In certain embodiments, this disclosure relates to methods of treating cancer comprising administering a nucleic acid or vector encoding interleukin-37 to a subject diagnosed with cancer and administering T cells expressing a chimeric antigen receptor to the subject. In certain embodiments, this disclosure relates to methods of treating cancer comprising administering a nucleic acid or vector encoding interleukin-37 and a chimeric antigen receptor to a subject diagnosed with cancer.

The present disclosure provides compositions and methods for expanding T cells or tumor infiltrating lymphocytes (TILs) in vitro. K562 feeder cells engineered to express a costimulatory molecule (e.g., 41BB ligand (41BBL)) and either interleukin 21 (IL21) or interleukin 7 (IL7) can be used in a rapid expansion protocol (REP) step to expand the T cells or TILs. Thus, provided herein is a culture comprising T-cells or TILs and modified K562 feeder cells. The T cells can be modified to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) or the TILs can be modified to express membrane-bound IL15 (mbIL15). The T cells or TILs can be expanded in vitro using aREP without the use of exogenous interleukin 2 (IL2), and the expanded cells can be used in adoptive cell therapy for treatment of cancer without concomitant use of an exogenous cytokine such as IL2.

The present disclosure relates to cells capable of co-expressing one or any combination of T cell receptors (TCR), CD8 polypeptides, interleukin 12 (IL-12) polypeptides, interleukin 15 (IL-15) polypeptides, and/or interleukin 18 (IL-18) polypeptides, and the use thereof in adoptive cellular therapy (ACT). The present disclosure further provides for modified CD8 sequences, IL-12 sequences, IL-15 sequences, IL-18 sequences, vectors, compositions, transformed T cells, and associated methods thereof.

An engineered immune cell, which expresses (i) a cell surface molecule that specifically recognizes a ligand, (ii) an exogenous interleukin, and (iii) an exogenous Flt3L, XCL2, and/or XCL1; the engineered immune cell can be used for treating cancer, infection, or autoimmune diseases; and compared with a traditional engineered immune cell, the engineered immune cell has significantly improved tumor killing activity.

Provided herein are mutants of estrogen receptor alpha ligand binding domain (ER-LBD), and chimeric proteins including such mutant ER-LBD. Also provided are methods of modulating transcription and modulating localization of such chimeric proteins.

Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.

The present invention provides novel fusion proteins comprising two cytokines: interleukin-6 (IL-6) and interleukin-1 beta (IL-1?). Methods of using the fusion proteins to activate target cells or treat a disease are also provided.