Relapse in adoptive cell transfer of CAR-T cells is often the result of CAR-T cells disappearance. Disclosed herein a method for enhancing CAR-T cell therapy in a subject, comprising administering to a subject undergoing adoptive cell transfer of therapeutic CAR-T cells an Akt inhibitor in an amount effective to increase the persistence of the CAR-T cells. As a consequence, a subject treated with a combination of CAR-T cells and an Akt inhibitor is less likely to relapse. Therefore, also disclosed herein is a method for treating a subject, comprising adoptively transferring to the subject an effective amount of a composition comprising a CAR-T cell, and administering to the subject an Akt inhibitor in an amount effective to increase the persistence of the CAR-T cells.

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.

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.

The present disclosure relates to engineered T cells and methods of making and using the same, as well as reagents for making the engineered T cells.

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.

An isolated cytotoxic T-lymphocyte (CTL), said CTL being a tolerance inducing cell and substantially depleted of alloreactivity, and wherein said CTL does not comprise a central memory T-lymphocyte (Tcm) phenotype, the CTL being transduced to express a cell surface receptor comprising a T cell receptor signaling module, is disclosed. Methods of generating same and using same are also disclosed.

Provided herein are compositions and methods for targeted treatment of Aspergillus-associated diseases and disorders in mammals, such as diseases and disorders associated with Aspergillus infection.

Provided herein are compositions and methods for regulating expression of effector molecules using regulatable transcription factors and/or activation inducible promoters.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.