Abstract: The present invention discloses recombinant vaccinia virus (VV) virions that are resistant to antiviral defenses and have enhanced anti-tumor activities. In one embodiment, the recombinant VV comprise one or more variant VV proteins that have mutations at one or more neutralizing antibody epitopes, thereby conferring viral escape from the neutralizing antibodies. In another embodiment, the recombinant VV is resistant to complement-mediated neutralization due to the expression of a regulator of complement activation (e.g. CD55). In another embodiment, the recombinant VV has enhanced anti-tumor activities due to the expression of bi-specific antibodies co-targeting cancer cells and immune effector cells, or the expression of a polypeptide blocking the PD-1 pathway. The recombinant vaccinia virus virions can be used to treat cancer in a subject.

Abstract: The invention provides a Natural Killer Cell, which may be a NK92 cell that is modified to express one or more types of Chimeric Antigen Receptor (CAR) on its surface, and administering said cell to a subject for a cancer treatment. Said engineered CAR comprises an antigen binding domain, which may bind CD19 or GD2, a transmembrane domain, a co-stimulatory signaling region, which may be all or a portion or variant of 2B4, and a signaling domain, which may be all or a portion or variant of CD3?.

Abstract: The invention includes compositions and methods for enhancing immunopotency of an immune cell by way of inhibiting a negative immune regulator in the cell. The present invention provides vaccines and therapies in which antigen presentation is enhanced through inhibition of negative immune regulators. The present invention also provides a mechanism to break self tolerance in tumor vaccination methods that rely on presentation of self tumor antigens.

Abstract: The invention includes compositions and methods for enhancing immunopotency of an immune cell by way of inhibiting a negative immune regulator in the cell. The present invention provides vaccines and therapies in which antigen presentation is enhanced through inhibition of negative immune regulators. The present invention also provides a mechanism to break self tolerance in tumor vaccination methods that rely on presentation of self tumor antigens.