The present invention relates to the field of immunology, molecular biology and therapeutics. In particular, the invention relates to novel artificial feeder cells for activation and expansion of natural killer (NK) cells. The artificial feeder cell expresses endogenous ligands (HLA C1, C2, 5 and Bw4 type) for killer cell immunoglobulin-like receptors (KIRs), non-KIR binding Bw6 ligand, endogenous HLA-E-ligand for inhibitory NKG2A receptor, and comprises at least one stimulatory cytokine either membrane bound or secreted or at least one co-stimulatory ligand where those ligands and cytokines each specifically bind to a cognate receptor on a NK cell of interest, thereby mediating expansion of the NK cell. The invention can be used as an “off the 10 shelf” artificial feeder cell that can be readily designed to expand a NK cell or a NK subset of interest and also specifically expand NK cells modified with a chimeric antigen receptor (CAR). By genetically introducing or knockdown of candidate genes, the artificial feeder cell of the invention can be used to identify the stimulatory, co-stimulatory, and any other factors that mediate growth, expansion and cytotoxicity of a NK cell. Thus, the present invention provides 15 powerful tools for development of novel therapeutics where activation and expansion of the NK cell and of the CAR-NK cell can provide a benefit.

The present invention relates to the field of immunology, molecular biology and therapeutics. In particular, the invention relates to novel artificial feeder cells for activation and expansion of natural killer (NK) cells. The artificial feeder cell expresses endogenous ligands (HLA C1, C2, 5 and Bw4 type) for killer cell immunoglobulin-like receptors (KIRs), non-KIR binding Bw6 ligand, endogenous HLA-E-ligand for inhibitory NKG2A receptor, and comprises at least one stimulatory cytokine either membrane bound or secreted or at least one co-stimulatory ligand where those ligands and cytokines each specifically bind to a cognate receptor on a NK cell of interest, thereby mediating expansion of the NK cell. The invention can be used as an “off the 10 shelf” artificial feeder cell that can be readily designed to expand a NK cell or a NK subset of interest and also specifically expand NK cells modified with a chimeric antigen receptor (CAR). By genetically introducing or knockdown of candidate genes, the artificial feeder cell of the invention can be used to identify the stimulatory, co-stimulatory, and any other factors that mediate growth, expansion and cytotoxicity of a NK cell. Thus, the present invention provides 15 powerful tools for development of novel therapeutics where activation and expansion of the NK cell and of the CAR-NK cell can provide a benefit.

The present invention relates to T cells, in particular a non-activated T cell, comprising an exogenous nucleic acid encoding a T cell Receptor (TCR) specific for a virus. An embodiment of the invention is directed to a non-activated (resting) T cell expressing Hepatitis B virus (HBV) envelope s183-191 TCR capable of inhibiting viral replication and which shows reduced expression of perforins and/or granzymes in response to stimulation as compared to an activated T cell expressing the said TCR. Also encompassed are methods for producing such cells, compositions, pharmaceutical compositions and kits comprising such cells and medical uses thereof.

The present invention relates to T cells, in particular a non-activated T cell, comprising an exogenous nucleic acid encoding a T cell Receptor (TCR) specific for a virus. An embodiment of the invention is directed to a non-activated (resting) T cell expressing Hepatitis B virus (HBV) envelope s183-191 TCR capable of inhibiting viral replication and which shows reduced expression of perforins and/or granzymes in response to stimulation as compared to an activated T cell expressing the said TCR. Also encompassed are methods for producing such cells, compositions, pharmaceutical compositions and kits comprising such cells and medical uses thereof.

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.

The present disclosure provides compositions and methods for improving an antitumor response against non-inflamed solid tumors. Methods of this disclosure include use of an eIF4A inhibitor to promote infiltration of antitumor lymphocytes into a non inflamed solid tumor. Methods of treating cancer associated with a non-inflamed solid tumor are also provided.

The present disclosure provides compositions and methods for improving an antitumor response against non-inflamed solid tumors. Methods of this disclosure include use of an eIF4A inhibitor to promote infiltration of antitumor lymphocytes into a non inflamed solid tumor. Methods of treating cancer associated with a non-inflamed solid tumor are also provided.

There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.