Provided herein are T cells expressing a chimeric antigen receptor (CAR) targeted to B cell activating factor receptor (BAFF-R). The CAR targeted to BAFF-R (BAFF-R CAR) described herein includes a domain that binds BAFF-R. Methods of making and using the BAFF-R CAR are also provided.

Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Described herein is a cell comprising a feedback circuit. In some embodiment, the circuit may comprise: (a) a first polypeptide that is activated by an external stimulus and, downstream from the first polypeptide: (b) a target protein and (c) a fusion protein comprising: (i) a domain that binds to the target protein of (b) and (ii) a degron or E3 ligase-recruiting domain. In these embodiments, the first polypeptide of (a), in its activated form, independently activates the expression of (b) and (c); and the fusion protein of (c) binds to the first polypeptide of (a), thereby causing degradation of the first polypeptide in trans. Methods using the cell are also provided.

The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.

Described herein, are the extended and newly discovered novel formulations of FL118 for cancer treatment to preclude, eliminate or reverse cancer phenotypes and treatment resistance.

The invention relates to novel chimeric antigen (CAR) mRNA molecules, the methods of generating the molecules and methods of treating cancer with the molecules.

Modified T cells comprising ectopic CD40 proteins (such as chimeric CD40 proteins including a CD40 extracellular domain and a heterologous intracellular domain) are provided. Also provided are compositions, including pharmaceutical formulations, comprising the modified T cells, and methods for increasing T cell-mediated tumor cell-specific cytotoxicity using the same. Methods of treating a subject with cancer including administering to the subject the modified T cells, thereby activating an innate immune response and/or an adaptive immune response in the subject are also provided.

Vector compositions comprising a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a chimeric antigen receptor (CAR) are provided.

The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.