Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion in vivo and/or in vitro. For example, a cell may comprise a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR may recognize a surface molecule of a blood cell.

The present invention contemplates mRNA, episomal and retroviral genomic gene therapy based short-term, intermediate or long-term vaccine, immunization, immune protection or cancer—that can also be administered as a retroviral genomic gene therapy both in vivo and ex vivo—method to provide epithelial and hematological protection to humans to protect against cancer especially carcinomas, pandemic and non-pandemic viruses, bacterial infections, allergens or the cause of allergic reactions, systemic pathological conditions, cancer and anti-biowarfare agents (e.g. natural and unnatural viruses and toxins) where mucosal immunity and for some diseases hematological immunity is achieved through mRNA, episomal or genomic integrated lentiviral and gammaretroviral vector expression of dimeric immunoglobulin A1 (dIgA1), dimeric immunoglobulin A2 (dIgA2) and engineered variants. Additionally, in some embodiments a method to agglutinate cancers including carcinomas and hematological cancers to prevent metastasis with polymeric immunoglobulin A and dimeric immunoglobulin A and engineered variants. The present invention provides methods, immunoglobulin compositions and vector constructs to express potent immunoglobulins that are derived from human blood of a human currently infected with, affected by, exposed to or recovered from any of a wide range of allergens or the cause of allergic reactions, pathogens (including, viruses, virus mutants, bacterial infections and fungi) and systemic pathological ailments (including cancer and other disorders), developed from phage display technology or mice or other non-human vertebrates with engineered immune systems or humanized immune systems, transgenic mice or chimeric antibodies a fusion of non-human vertebrates (e.g. mouse or rabbit), mouse antibody V-regions, human antibodies. The immunoglobulin compositions include the heavy chain variable, diversity and joining (VDJ or Variable Heavy Region genes) segment immunoglobulin DNA and/or polypeptide sequence from humans identified to have therapeutically relevant affinity immunoglobulins against the antigen, protein or proteins of interest and either to use the exact immunoglobulin heavy chain and light chain polypeptide sequences identified from the B-cell that produced them or to modify or engineer some of the immunoglobulin heavy chain and light chain constant domains to modulate effector functions. Although, ideally there are no changes made to the immunoglobulins light and heavy chains as identified from the B-cell that produced them. Modifications may occur at the Hinge region, Constant Heavy 2 (C.sub.H2) domain and Constant Heavy 3 (C.sub.H3) domain for the immunoglobul

A system for inducing activity of immune cells, comprises a chimeric antigen receptor, a T cell receptor, and various combinations thereof.

Provided are a GPC3 and ASGPR1 double-targeted transgenic immune effector cell and use thereof. The cell is an immune effector cell capable of identifying the gene modification of GPC3 and ASGPR1 simultaneously, and the cell can be used in the treatment of GPC3 and ASGPR1 double positive tumours, such as liver cancer.

Disclosed herein are cells expressing DUX4 including stem cells, differentiated cells thereof, primary T cells, and chimeric antigen receptor T cells, as well as related methods of their use and generation. In some embodiments, the cells disclosed herein do not express one or more MHCI and/or MHC II human leukocyte antigens. In some embodiments, such cells possess immune evasion properties.

The invention provides methods and compositions for perturbing gene expression in hematopoietic cell lineages in vivo.

A method, system, and apparatus for treating a patient with HIV. A vector can be modified from a thymidine kinase gene. The modified vector is expressed in the presence of tat RNA. The modified vector is then package and delivered to HIV-infected cells. The replication of HIV is inhibited by eliminating infected cells in the presence of Ganciclovir. Modified cells are then selected utilizing transient tat RNA transfection and GFP expression. Vector-modified stem cells are then selected for transplantation back into the patient, thereby producing a normal immune system in the patient when the modified vector remains dormant in the absence of HIV tat.

The invention provides for use of CRISPR-Cas systems to sort barcoded cells or molecules. Cells or nucleic acid molecules may be sorted from a heterogenous population by targeting a barcode of interest specific for a cell or cell progeny or nucleic acid molecule of interest.

Methods for treating a subject for arthritis are provided. Aspects of the methods include administration to the subject a rs419598/rs315952/rs9005-haplotype-informed therapeutic regimen. In some instances, the methods include administering to the subject a therapeutic regimen that antagonizes interleukin-1 (IL-1) activity and/or a disease modifying osteoarthritis drug (DMOAD) if the subject has been identified as having a TTG rs419598/rs315952/rs9005 haplotype. Also provided are compositions for use in practicing the methods.