The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with ?-secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with ?-secretase inhibitor can be used in, for example, adoptive immunotherapy.

The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.

Provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and their use in directing immune responses to target cells. The compositions have uses that include treating hyperproliferative disorders such as cancer. The provided methods generally include the use of a CAR cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or redirect CAR cell-mediated immune response in vitro and in vivo. In some embodiments, the CAR cell comprises a genetic modification to reduce or eliminate the expression of a targeted antigenic determinant.

Provided herein are methods of identifying genomic region(s) predictive of an outcome of treatment with a cell therapy and/or of a phenotype of function of the cells. In some embodiments, the methods include epigenetic and/or epigenomic analyses of the cells in connection with methods for preparing engineered cells for cell therapy and/or predicting response to a cell therapy, e.g., engineered cells for cell therapy. In some embodiments, the methods include steps to assess, characterize and analyze changes or modifications in an epigenetic property of gene region or regions, such as chromatin accessibility, nucleosome occupancy, histone modification, spatial chromosomal conformation, transcription factor occupancy and/or DNA methylation. In some embodiments, the epigenetic and/or epigenomic analysis includes determining the epigenetic properties of a cell, e.g., an engineered cell for cell therapy.

A method for assessing responsiveness of a subject to a treatment comprising T cells expressing a bivalent BCMA-targeting chimeric antigen receptor (CAR), comprising administering to the subject the T cells, and assessing the responsiveness of the subject to the treatment based on time length the subject maintains minimal residual disease (MRD) negative status.

Provided herein are BAFF-R antibodies as well as compositions and methods of making and using the same. The antibodies provided herein are, inter alia, useful for the treatment of cancer and autoimmune diseases.

Disclosed herein are genome-edited invariant natural killer T (iNKT) cells and methods of immunotherapy using them. In particular, the disclosure relates to engineered chimeric antigen receptor (CAR)-bearing INKT cells (CAR-iNKTs) and methods of using the same for the treatment of cancer.

Provided herein are lentiviral vectors comprising a mutated, heterologous envelope protein, a targeting protein, and at least one transgene for delivery to and expression by a cell characterized by the targeting protein. Also provided are methods and materials for producing the lentiviral vectors described herein, methods for transducing target cells, and cells transduced by lentiviral vectors according to the present disclosure.

The invention provides improved compositions for adoptive cell therapies for cancers. The invention generally provides improved vectors for generating T cell therapies and methods of using the same. More particularly, the invention provides salvage CARs, dimerizable salvage receptors, and their use in treating, preventing, or ameliorating cancers, and in particular preferred embodiments relapsed or refractory cancer. In various embodiments, a salvage chimeric antigen receptor (CAR) is provided comprising: an extracellular antigen binding domain; a multimerization domain; a transmembrane domain; one or more intracellular co-stimulatory signaling domains; and/or a primary signaling domain.

The invention provides a recombinant chimeric antigen receptor (CAR) gene, a vector containing the same, a CAR-T cell and a use thereof. The recombinant CAR gene comprises a nucleic acid sequence encoding an antigen-binding portion of a CD30 antibody, a transmembrane portion and a CD137 cytoplasmic functional region and a CD3zeta cytoplasmic functional region linked in any order; also provides a method of treating Hodgkin's lymphoma or anaplastic large cell lymphoma or other CD30-positive tumors using the CAR-T cells of the invention.