Nucleic acids encoding fusion proteins that contain an unwanted antigen and a leader sequence for cell secretion are described. Also described are expression cassettes, vectors, cells, and cell lines containing the nucleic acids, as well as methods of using the nucleic acids to treat autoimmune, allergic and other diseases and disorders, such as multiple sclerosis.

Embodiments of the disclosure encompass improvements on cell therapies by allowing the cells to be more effective for cancer treatment, including in a solid tumor microenvironment. In specific cases, the cells are modified to have reduced or inhibited levels of expression of T-Cell Death Associated Gene 8 (TDAG8), such as by CRISPR gene editing. In specific cases, the cells are further modified to express, for example, one or more engineered receptors, one or more cytokines, and optionally a suicide gene.

Embodiments of the disclosure encompass improvements on cell therapies by allowing the cells to be more effective for cancer treatment, including in a solid tumor microenvironment. In specific cases, the cells are modified to have reduced or inhibited levels of expression of T-Cell Death Associated Gene 8 (TDAG8), such as by CRISPR gene editing. In specific cases, the cells are further modified to express, for example, one or more engineered receptors, one or more cytokines, and optionally a suicide gene.

Methods and systems to reduce neurotoxicity associated with the treatment of CD19.sup.+ B-cell hyperproliferative disorders are disclosed. Neurotoxicity is reduced by the use of agents that protect CD19.sup.+ neurovascular pericytes and/or CD19.sup.+ vSMCs from attack by CD19-targeted therapy, and by modification of CD19-targeted therapy to avoid CD19.sup.+ pericytes and/or CD19.sup.+ vSMCs.

Provided is a host factor specific for hepatitis B virus (HBV) infection. The specific host factor CREBH can remarkably enhance HBV infection. The specific host factor can, on the one hand, enhance entry of HBV, and on the other hand, enhance transcription of HBV to some extent. In the CREBH regulatory pathway there is a specific host factor SCARF2. During HBV infection, an N-terminus EGF-like domain of SCARF2 plays a crucial role in the infection and entry of HBV. The two correlated specific host factors provide a new target for inhibiting HBV infection.

Provided is a host factor specific for hepatitis B virus (HBV) infection. The specific host factor CREBH can remarkably enhance HBV infection. The specific host factor can, on the one hand, enhance entry of HBV, and on the other hand, enhance transcription of HBV to some extent. In the CREBH regulatory pathway there is a specific host factor SCARF2. During HBV infection, an N-terminus EGF-like domain of SCARF2 plays a crucial role in the infection and entry of HBV. The two correlated specific host factors provide a new target for inhibiting HBV infection.

Disclosed herein are fusion proteins having a first domain that activates an antigen-presenting cell (APC) (e.g., a dendritic cell) by binding to an activation receptor of the APC, and a second domain that activates an immune effector cell (e.g., a T cell) by targeting a co-stimulatory signaling pathway of the immune effector cell, as well as polynucleotides that encode such fusion proteins. Disclosed herein are also genetically engineered immune effector cells expressing such fusion protein, methods of their production, and their uses in treatment of diseases such as cancers.

A multispecific nanobodies chimeric antigen receptor and T-cell engager includes an HLA-G nanobody chimeric antigen receptor and a bispecific T-cell engager. The HLA-G nanobody chimeric antigen receptor includes an HLA-G nanobodies unit, a transmembrane domain, and a CD3z signaling domain. The bispecific T-cell engager includes a PD-L1 nanobodies unit and a CD3e nanobody.

The present disclosure methods for identifying binding partners using cell surface display libraries, where the cells of the library display engineered peptides on their cell surfaces for identification of peptides that bind to targets of interest. The engineered peptides are preferably expressed in the cells under conditions that provide both secretion and display of the engineered peptides on the cell surfaces, thus providing access of the engineered peptides to identify potential binding pairs. The cell libraries cab be engineered using an automated editing system that provides for one or more targeted edits per cell.

Provided are a bifunctional fusion protein and pharmaceutical use thereof. Specifically, provided are a bifunctional fusion protein comprising an SIRPγ peptide variant and an anti-human PD-L1 antibody, an SIRPγ peptide variant, and pharmaceutical use thereof. The bifunctional fusion protein can specifically bind PD-L1 and CD47 to block the binding of PD-L1 or CD47 to a receptor or ligand thereof. In addition, also provided are preparation and application of the bifunctional fusion protein, and treatment of cancers and immune-related diseases.