Methods and systems for producing a protein of interest within a plant or a portion of a plant are provided herein. The method includes introducing one or more nucleic acid into the plant or the portion of the plant, the nucleic acid including a nucleotide sequence encoding the protein of interest and incubating the plant or the portion of the plant under conditions that permit the expression of the nucleotide sequence encoding the protein of interest. The method also includes adding a medium amendment including a calcium carbonate source, such as aragonite, to a medium environment of the plant.

The present invention is directed to novel PD-1-targeted IL-15/Rα-Fc fusion proteins comprising an IL-15/IL-15Rα Fc-fusion protein and a PD-1 antigen binding domain. The PD-1-targeted IL-15/Rα-Fc fusion proteins can be administered to a patient to treat cancer.

Disclosed is a chimeric antigen receptor with improved persistency.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.

Provided herein are compositions and methods for promoting hematopoietic cell cytotoxicity.

Provided are chimeric cytokine modified antibodies containing an ultralong CDR3, such as based on a bovine antibody sequence or a humanized sequence thereof, in which a portion of the CDR3 of the heavy chain is replaced by an interleukin (IL-15) or IL-2, and related antibodies. Among provided antibodies are chimeric IL-15 cytokine modified antibody molecules that are further linked or complexed with an extracellular portion of the IL15Rα, such as the IL15Rα sushi domain. Also provided are methods of making and using the chimeric cytokine modified antibodies.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL10R and/or a human or chimeric (e.g., humanized) IL10, and methods of use thereof.

Disclosed are chimeric stimulatory receptors (CSRs), cell compositions comprising CSRs, methods of making and methods of using same for the treatment of a disease or disorder in a subject.