Abstract: Recombinant oncolytic viruses that produce and secrete novel immunomodulatory fusion proteins are described. The fusion proteins encode a single chain variable fragment antibody (ScFv) that specifically binds PD-1 OR PD-L1 fused via an antibody Fc region to the ectodomain of the TGF? receptor II (TGF?RIIecto). The immunomodulatory fusion proteins have dual function: blocking inhibitory pathways mediated by PD-1/PD-L1 and blocking the immune-dampening activity of TGF?. In addition, dual gene oncolytic herpes simplex viruses (HSVs) are provided that include, in addition to a gene encoding an ScFv-Fc-TGF?RIIecto fusion protein, a gene encoding IL12, a T cell stimulatory factor.

Abstract: Described herein is a method of treating a cancer in an individual comprising administering a tyrosine kinase-like orphan receptor 1 (ROR1) antagonist and an epidermal growth factor receptor (EGFR) inhibitor. In some embodiments, the ROR1 antagonist is cirmtuzumab. In some embodiments, the EGFR inhibitor is osimertinib. In some embodiments, the cancer is a lung cancer such as a non-small cell lung cancer.

Abstract: There is disclosed a recombinant pharmaceutical composition comprising a large plurality of recombinant immunoglobulins made by expression of a wide diversity of antibodies from a recombinant antibody library, preferably obtained from a wide diversity of human sources, synthetic or semi-synthetic germline immunoglobulin sequences, or a combination thereof, and then purified. Mammalian cell expression antibody libraries normally produce antibodies with significant diversity or different antibodies that bind to different targets. There is further disclosed a recombinant pharmaceutical composition made from a mammalian expression library configured to excrete, rather than display their antibodies on the cell surface, and then purified to form the pharmaceutical composition from the excreted antibodies.