The invention provides methods of treating CD-19 positive malignancies in human subjects with suitable doses of switchable CAR-T cells and complementary switch molecules.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and a membrane bound IL-12 and methods of making and using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

Nucleic acid molecules encoding an IL-15 domain and a chimeric antigen receptor (CAR) that targets cells expressing prostate stem cell antigen (PSCA) are provided as well as polypeptides encoded thereby. Vectors and immune cells (e.g., NKT cells) containing the nucleic acid molecules also are disclosed, as well as methods for their use.

This invention relates to methods and compositions directed to mobilizing a cell in a subject by blocking CXCR4, a beta-adrenergic receptor, a GPCR, or any combination thereof. In some embodiments, the cell is a stem cell. In some embodiments, the cell is an immune cell.

The present disclosure provides improved methods of producing engineered T cells that express an exogenous gene (e.g., CAR-T cells). T cells that express an exogenous gene and compositions comprising the same of the present technology are useful for treating various diseases, e.g., infection, autoimmune diseases, and tumors.

The present invention relates to a fusion protein that provides for maintenance of regulatory T-cells that are polyclonal, e.g. natural isolated antigen-specific Treg cells, and/or Treg cells generated by introduction of a nucleic acid construct for expression of FOXP3, and/or Treg cells which express a chimeric antigen receptor (CAR), which Treg cells in contact with the cognate antigen are activated for suppressive activity, as well as to Treg cells that express the fusion protein, wherein the Treg cells are polyclonal or the Treg cells express a CAR. The fusion protein comprises or consists of an optional secretory leader peptide, IL-2, preferably a linker peptide, and a membrane-spanning anchor, which fusion protein is also termed membrane-bound IL-2.

The present disclosure relates to a molecular delivery system that facilitates the internalization of LNPs into a specific target of choice, such as a specific cell type, ex vivo and/or in vivo. The present disclosure also relates to methods, molecules, and compositions for enhancing the targeted delivery of compounds within a living system. In particular, embodiments provided herein relate to methods, molecules, and compositions for the targeted delivery of lipid nanoparticles containing therapeutic molecules into a cell or system of choice, such as a T cell. The present disclosure also relates to methods of administering the enhanced targeting system to a patient or system, compositions for use in such methods, and further methods of use of the targeting system as part of T cell-based immunotherapy.

An orally bioavailable benzofuran is provided which possesses in vitro and in vivo capabilities able to overcome issues in loading of antigenic peptide on major histocompatibility class I complexes, including on the surface of professional antigen presenting cells. The design of immunotherapies such as dendritic cell vaccines, optimal binding of the antigenic peptides to MHC class I complexes is a major challenge. Current therapeutic peptide loading is expensive, labor-intensive, or requires in vitro manipulation. Models demonstrate that the benzofuran enhances T-cell activation through increased peptide binding to cell surface MHC class I complexes. Molecular docking studies indicate the benzofuran binds the F pocket of MHC class I in a similar manner to high-affinity peptides and TAPBPR, aiding in the targeted loading of exogenous peptides. The therapeutic potential was demonstrated when using PLGA particles of BzF were injected intramuscularly, and significantly inhibited the development of E.G7-OVA tumors.

The invention provides personal neoantigen vaccines, and uses thereof. The invention also provides markers MX1 and PPP1R15A, and uses thereof. The invention also provides sets of biomarkers, and uses thereof.

Provided herein are methods of treating cancer in a subject in need thereof by administering an anti-BCMA CAR-T cell and a GPRC5DCD3 bispecific antibody. In some embodiments, the subject has relapsed and/or refractory multiple myeloma. In some embodiments, the subject has received at least one prior line of therapy. In some embodiments, the subject has newly diagnosed multiple myeloma and is transplant ineligible.