Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and/or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

Disclosed are anti-C3d antibodies or fragments thereof. Also disclosed are methods of killing cancer cells, methods of preparing anti-C3d antibodies, and pharmaceutical compositions.

The application provides modified immune effector cells wherein a Lysine Demethylase 4A (KDM4A) gene or gene product is modified in the cell so that the expression and/or function of KDM4A in the cell is reduced or eliminated. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

The application provides modified immune effector cells wherein a Lysine Demethylase 4A (KDM4A) gene or gene product is modified in the cell so that the expression and/or function of KDM4A in the cell is reduced or eliminated. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Disclosed herein are immune effector cells for use in adoptive cell transfer that have chemically- or genetically-inhibited PDHB (Pyruvate dehydrogenase E1 subunit beta) expression or activity. Also disclosed are methods of inhibiting or ablating PDHB expression in immune effector cells ex vivo and methods of using these cells to treat subjects with cancer. In some embodiments, the immune effector cells are further treated with a TIMS inhibitor or genetically engineered to ablate TIM3 expression. In some embodiments, the immune effector cells are further treated with a LAGS inhibitor or genetically engineered to ablate LAG3 expression. In some cases, the PDHB gene is disrupted by insertion of the gene encoding the chimeric receptor into the PDHB gene loci of the cell. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor.

Disclosed herein are immune effector cells for use in adoptive cell transfer that have chemically- or genetically-inhibited PDHB (Pyruvate dehydrogenase E1 subunit beta) expression or activity. Also disclosed are methods of inhibiting or ablating PDHB expression in immune effector cells ex vivo and methods of using these cells to treat subjects with cancer. In some embodiments, the immune effector cells are further treated with a TIMS inhibitor or genetically engineered to ablate TIM3 expression. In some embodiments, the immune effector cells are further treated with a LAGS inhibitor or genetically engineered to ablate LAG3 expression. In some cases, the PDHB gene is disrupted by insertion of the gene encoding the chimeric receptor into the PDHB gene loci of the cell. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors or additional cells in combination therapies.

Engineered tunable chimeric receptor/ligand pairs, and methods of use thereof, are provided.

Engineered tunable chimeric receptor/ligand pairs, and methods of use thereof, are provided.

An anti-CD371 (anti-CLL-1) chimeric antigen receptor (CAR), engineered immune cells comprising the CAR, as well as therapeutic compositions, therapeutic methods and companion diagnostic methods are disclosed herein.