Abstract: A Twin Immune Cell Engager (TWICE) is a kit or composition for treating cancer comprising a first component and second component. Each component comprises a targeting moiety that binds a tumor antigen expressed by the cancer or an antigen expressed by a non-cancer cell in the tumor microenvironment. In some embodiments, the first and second components each comprise an immune cell binding domain capable of immune cell binding activity when binding the immune cell binding domain in the other component, and a complementary binding domain capable of binding to a complementary antigen when binding the complementary binding domain in the other component. In some embodiments, the first and/or second components comprise a complementary functional domain with activity when targeted to the cancer cell or its microenvironment. The present TWICE complexes offer a unique ability to combine multiple functions into a two-component complex that becomes activated in the tumor microenvironment.

Abstract: A Twin Immune Cell Engager (TWICE) is a kit or composition for treating cancer comprising a first component and second component. Each component comprises a targeting moiety that binds a tumor antigen expressed by the cancer or an antigen expressed by a non-cancer cell in the tumor microenvironment. In some embodiments, the first and second components each comprise an immune cell binding domain capable of immune cell binding activity when binding the immune cell binding domain in the other component, and a complementary binding domain capable of binding to a complementary antigen when binding the complementary binding domain in the other component. In some embodiments, the first and/or second components comprise a complementary functional domain with activity when targeted to the cancer cell or its microenvironment.

Abstract: A targeted T-cell engaging agent for treating a condition characterized by the presence of unwanted cells includes (a) a targeting moiety that is capable of targeting the unwanted cells; (b) a first T-cell engaging domain capable of T-cell engaging activity when binding a second T-cell engaging domain, wherein the second T-cell engaging domain is not part of the agent; (c) at least one inert binding partner capable of binding to the first T-cell engaging domain such that the first T-cell engaging domain does not bind to the second T-cell engaging domain unless the inert binding partner is removed; and (d) at least one cleavage site separating the first T-cell engaging domain and the inert binding partner, wherein the cleavage site is: (i) cleaved by an enzyme expressed by the unwanted cells; (ii) cleaved through a pH-sensitive cleavage reaction inside the unwanted cell; (iii) cleaved by a complement-dependent cleavage reaction; or (iv) cleaved by a protease that is colocalized to the unwanted cell by a target

Abstract: A targeted T-cell engaging agent for treating a condition characterized by the presence of unwanted cells includes (a) a targeting moiety that is capable of targeting the unwanted cells; (b) a first T-cell engaging domain capable of T-cell engaging activity when binding a second T-cell engaging domain, wherein the second T-cell engaging domain is not part of the agent; (c) at least one inert binding partner capable of binding to the first T-cell engaging domain such that the first T-cell engaging domain does not bind to the second T-cell engaging domain unless the inert binding partner is removed; and (d) at least one cleavage site separating the first T-cell engaging domain and the inert binding partner, wherein the cleavage site is: (i) cleaved by an enzyme expressed by the unwanted cells; (ii) cleaved through a pH-sensitive cleavage reaction inside the unwanted cell; (iii) cleaved by a complement-dependent cleavage reaction; or (iv) cleaved by a protease that is colocalized to the unwanted cell by a target

Abstract: A targeted T-cell engaging agent for treating a condition characterized by the presence of unwanted cells includes (a) a targeting moiety that is capable of targeting the unwanted cells; (b) a first T-cell engaging domain capable of T-cell engaging activity when binding a second T-cell engaging domain, wherein the second T-cell engaging domain is not part of the agent; (c) at least one inert binding partner capable of binding to the first T-cell engaging domain such that the first T-cell engaging domain does not bind to the second T-cell engaging domain unless the inert binding partner is removed; and (d) at least one cleavage site separating the first T-cell engaging domain and the inert binding partner, wherein the cleavage site is: (i) cleaved by an enzyme expressed by the unwanted cells; (ii) cleaved through a pH-sensitive cleavage reaction inside the unwanted cell; (iii) cleaved by a complement-dependent cleavage reaction; or (iv) cleaved by a protease that is colocalized to the unwanted cell by a target