Abstract: Described herein are methods and compositions for selective activation of cells using variant cytokine receptor and cytokine pairs, wherein the cytokine receptors comprise an extracellular domain (ECD) of granulocyte-colony stimulating factor receptor (G-CSFR). In certain embodiments, the methods and compositions described herein are useful for exclusive activation of cells for adoptive cell transfer therapy. Thus, included herein are methods of producing cells expressing variant receptors that are selectively activated by a cytokine that does not bind its native receptor. Also disclosed herein are methods of treating a subject in need thereof, comprising administering to the subject cells expressing an variant receptor comprising an extracellular domain of G-CSFR and co-administering a variant cytokine that activates the variant receptor.

Abstract: The present disclosure provides fusion proteins with a multifunctional biologic design for programmed target engagement. In certain embodiments, the fusion proteins described herein provide for concurrent target antigen engagement and immune checkpoint or costimulatory receptor targeting. In certain aspects, the fusion protein is masked from presenting any on-target off-tissue action (i.e., toxicity) associated with target engagements. In certain embodiments, the fusion proteins provide a masked antigen binding domain as well as a masked immunomodulatory target binding domain, such that the programmed activation of one binding functionality results in the activation of the other binding functionality as well, thereby yielding a bispecific molecule. Thus, the disclosure also provides for methods of masking and conditional activation of antigen binding domains in specific target tissue setting and targeting and activation of immunomodulatory targets without severe adverse toxicity effects.

Abstract: Described herein are antibody constructs comprising a 4- 1BB binding domain and an anti-Folate Receptor a (FRa) antigen- binding domain, wherein the 4-1BB-binding domain and the FR? antigen-binding domain are linked directly or indirectly to a scaffold. The scaffold may be an Fc construct with modifications that reduce its ability to mediate effector function. The antibody constructs are used in the treatment of a subject having cancer.

Abstract: The present disclosure relates to masked IL12 fusion proteins, compositions comprising the same and methods of using the compositions for the treatment of a variety of diseases including cancer.

Abstract: Described herein are antibody constructs comprising a 41-1BB binding domain and an antigen-binding domain that binds to a tumor-associated antigen (TAA), wherein the 4-1BB-binding domain and the TAA antigen-binding domain are linked directly or indirectly to a scaffold. The scaffold may be an Fc construct with modifications that reduce its ability to mediate effector function.