The present disclosure provides compositions of genetically modified cells that are hypoimmunogenic. The present disclosure also provides methods of making hypoimmunogenic cells and using hypoimmunogenic cells for the treatment of cancer and autoimmune conditions.

The present invention provides recombinant TIM-4 fusion proteins comprising an extracellular domain of TIM-4 and at least one co-stimulatory domain. Also provided are cells comprising the fusion protein and methods of making and using the same.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Activity-inducible fusion proteins whose activity is post-translationally regulated utilizing a hsp90 binding domain and a drug molecule are described. In the absence of the drug molecule, the activity-inducible fusion proteins are inactivated but can be activated by a relevant physiological parameter in the presence of the drug molecule. Examples of the activity-inducible fusion proteins include chimeric antigen receptors (CAR) wherein the relevant physiological parameter is antigen binding.

The disclosure relates to immune cells comprising one or more vectors comprising a nucleic acid sequence encoding a chimeric antigen receptor specific for CD19 and a nucleic acid sequence encoding an enhancer of T cell priming (e.g., IL-18), compositions comprising the T cells, and methods of generating and/or using the T cells to treat diseases associated with the expression of CD19.

Described herein are methods using CRISPR-Cas9 and DNA templates that can generate chimeric antigen receptors (CARs) on T cells to target the cell surface protein urokinase Plasminogen Activator Receptor (uPAR) on senescent cells. Also described are methods of preparing CAR T cells, their use to treat neurodegenerative disease, stroke, craniocerebral trauma and/or accident, or elderly individuals in need of treatment for aging.

The present invention provides a novel chimeric antigen receptor, comprising an antigen-binding region, a transmembrane domain, a costimulatory domain, an intracellular signaling domain, and an additional signaling region. The additional signaling region consists of a ?c chain or an intracellular region thereof. The present invention also provides an engineered immune cell comprising the novel chimeric antigen receptor of the present invention and a pharmaceutical composition thereof, and use of the engineered immune cell/pharmaceutical composition for treating cancers.

The disclosure provides an antibody fusion protein comprising (i) heavy chains comprising variable region sequences comprising the amino acid sequence of SEQ ID NO: 1 and (ii) light chains comprising variable region sequences comprising the amino acid sequence of SEQ ID NO: 8, wherein the light chains are fused at the C-terminus to an A1-A2 domain comprising the amino acid sequence of SEQ ID NO: 11. Nucleic acids encoding all or part of the antibody fusion protein are provided, as well as methods of using the antibody fusion protein in the treatment of, e.g., CD20-positive cancers. The disclosure further provides a mutant A1-A2 domain peptide.

The disclosure provides an antibody fusion protein comprising (i) heavy chains comprising variable region sequences comprising the amino acid sequence of SEQ ID NO: 1 and (ii) light chains comprising variable region sequences comprising the amino acid sequence of SEQ ID NO: 8, wherein the light chains are fused at the C-terminus to an A1-A2 domain comprising the amino acid sequence of SEQ ID NO: 11. Nucleic acids encoding all or part of the antibody fusion protein are provided, as well as methods of using the antibody fusion protein in the treatment of, e.g., CD20-positive cancers.