A number of medical disorders are caused by either an insufficiency of a gene product or a defective gene product. Gene therapy can be used to provide a sufficient amount of a gene product when a disorder is caused by an insufficiency and can also be used to inactivate genes that produce defective gene products. Examples of disorders that can be treated by providing a sufficient amount of a gene product include lysosomal storage diseases, clotting disorders, diabetes, and alpha-1 antitrypsin deficiency. Systems and methods to produce B cells that express selected antibodies and gene products are described. The systems and methods can be used to provide prolonged and tunable expression of the gene products for the treatment of diseases such as lysosomal storage diseases, clotting disorders, diabetes, or other protein deficiencies.

The disclosure relates to fusion proteins comprising a tBID polypeptide and a steroid hormone receptor domain, and methods of using same to induce apoptosis in cells.

The disclosure relates to fusion proteins comprising a tBID polypeptide and a steroid hormone receptor domain, and methods of using same to induce apoptosis in cells.

A method of inhibiting CXCL1 in one or more natural killer (NK) cells in a subject is provided. The method involves administering one or more pharmaceutically effective doses of metformin to the subject. In another embodiment of the invention, a pharmaceutical composition useful for increasing natural killer cell activity in a subject is provided. The composition includes pembrolizumab, a CXCR2 inhibitor and a pharmaceutically acceptable excipient.

A method of inhibiting CXCL1 in one or more natural killer (NK) cells in a subject is provided. The method involves administering one or more pharmaceutically effective doses of metformin to the subject. In another embodiment of the invention, a pharmaceutical composition useful for increasing natural killer cell activity in a subject is provided. The composition includes pembrolizumab, a CXCR2 inhibitor and a pharmaceutically acceptable excipient.

Disclosed are methods of conditioning subjects who receive, are receiving, or have received an agent for in vivo reprogramming of immune cells in order to improve the efficiency of the in vivo reprogramming and/or the overall therapeutic effect of the treatment. Also disclosed are nanoparticle compositions for providing the conditioning agent(s). The conditioning agent can be provided prior to, concurrently with, or after administration of the in vivo reprogramming agent depending on the conditioning agent. The conditioning regimens are useful in combination with in vivo reprogramming of immune cells to treat hematologic cancers and solid tumor, fibrotic disorders, and B cell or T cell mediated autoimmunity, chronic infection. Some conditioning regimens are also useful in combination with other cancer treatments.

Disclosed are methods of conditioning subjects who receive, are receiving, or have received an agent for in vivo reprogramming of immune cells in order to improve the efficiency of the in vivo reprogramming and/or the overall therapeutic effect of the treatment. Also disclosed are nanoparticle compositions for providing the conditioning agent(s). The conditioning agent can be provided prior to, concurrently with, or after administration of the in vivo reprogramming agent depending on the conditioning agent. The conditioning regimens are useful in combination with in vivo reprogramming of immune cells to treat hematologic cancers and solid tumor, fibrotic disorders, and B cell or T cell mediated autoimmunity, chronic infection. Some conditioning regimens are also useful in combination with other cancer treatments.

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

The disclosure provides methods for promoting affinity maturation, and in particular in vivo affinity maturation, of antibodies. The disclosure also provides a system of affinity maturation of an antibody as well as compositions comprising antibodies generated from methods described herein and polynucleotides encoding such systems.