A recombinant natural killer (NK) cell or T-cell composition is transfected with a nucleic acid encoding i) a homing receptor; ii) an antigen binding protein (ABP) or a chimeric antigen receptor (CAR) that specifically binds a target antigen; iii) an Fc Receptor; and/or iv) a secreted immune modulator selected from a TGFβ inhibitor and/or IL-12, where the recombinant cell is gamma (γ)-irradiated conferring inhibition of cell proliferation with transient activity of the transfected molecules including the secreted immune modulators for up to 72 hours.

The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.

The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising chimeric antigen receptors (CARs) capable of binding human IL13R2. Also provided are bispecific CARs, parallel CARs, tandem CARs, BiTEs, BiTE/CARs, and BiTE/BiTEs. Compositions and methods of treatment are also provided.

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.

A recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR), a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. A recombinant nucleic acid expression construct encoding the CAR specifically recognizes CD44v6, and includes a PD1 checkpoint inhibitory molecule, and an immune stimulating cytokine. Further aspects relate to genetically modified cells, including a recombinant nucleic acid expression construct encoding the CAR, wherein the cells are preferably immune cells, more preferably NK cells or cytotoxic T lymphocytes or T helper cells. Medical use of the cells may be in the treatment of a medical disorder associated with the presence of pathogenic cells expressing CD44v6, preferably cancer cells, more preferably cancer stem cells of solid or liquid malignancies.

The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

Compositions of TNF family of cytokines in covalently linked trimeric forms are disclosed. The resulting fusion proteins are secreted as disulfide bond-linked homotrimers, which are more stable in structure and therapeutically more efficacious than their native counterparts.

Compositions of TNF family of cytokines in covalently linked trimeric forms are disclosed. The resulting fusion proteins are secreted as disulfide bond-linked homotrimers, which are more stable in structure and therapeutically more efficacious than their native counterparts.