The present invention relates to the treatment or management of autoimmune disorders, organ rejection and cancers utilizing CAR constructs that bind to T-cell surface antigens or B-cell or plasma surface antigens or both.

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.

An endogenous chimeric antigen receptor (ECAR) has an antigen-binding domain that is an endogenous protein molecule. The engineered immune cells expressing the ECAR can kill a variety of cells specifically and selectively.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. NK cells have effector activity within the TME, under continuous ligand exposure. NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. We created NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3 to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PDL1+ target cells.

The invention provides recombinant CD47 engager receptor proteins comprising an intracellular domain that enhances an immune response in a cell when the CD47 engager receptor protein binds to CD47 on a target cell. The invention also provides cells comprising the CD47 engager receptor proteins. The CD47 engager receptor protein may be a switched Signal Regulatory Protein Alpha (SIRP) receptor (SIRP switch receptors) and cells that comprise them (SIRP switch cells). SIRP switch receptors recognize CD47 on target tumor cells and transmit an intracellular signal within the SIRP switch cells that upregulates natural killer cell (NK), T cell, and macrophage activity. The result is increased tumor cell killing.

The present invention relates to chimeric transmembrane immunoreceptors, named zetakines, comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targetting domain of the IL-13R2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

One aspect of the present application relates to a recombinant cell comprising a chimeric antigen receptor and shRNA targeted to inhibit the life cycle of HIV. Another aspect of the present application relates to a chimeric antigen molecule, the extracellular region of which is from or comprising the extracellular region of human CD4 molecule, the transmembrane region of which is from or comprising the transmembrane domain of CD8, and a recombinant cell comprising the above chimeric antigen molecule. The above recombinant cell can be used to treat HIV infection, and have stronger comprehensive killing efficacy, longer effective time, and less risk of causing cytokine storm in the environment of HIV infection.

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.

Described are chimeric lactate receptors that act a molecular switches. A chimeric lactate receptor comprises a lactate receptor linked to one or more intracellular signaling domains. Also described are nucleic acids encoding the chimeric lactate receptors, T cell expressing the chimeric lactate receptors, and method of using the T cells to treat cancer.

The invention is in the field of immunotherapy. The present application provides modified RELA protein which are useful for inducing or promoting interferon expression by immune cells, in particular T cells. The invention enables the production of immune cells with an activated or enhanced interferon metabolism. The present application also relates to immune cells, in particular T cells, comprising and/or expressing a modified RELA protein according to the invention, such cells having an activated interferon metabolism. The present invention also provides in vitro and/or ex vivo method of preparing immune cells, in particular T cells, useful in immunotherapy. The invention also relates to methods for treating a patient, in particular a patient who has a cancer or an infectious disease, in particular an infection by a virus.