Abstract: Provided are compositions and methods for treating a solid or hematological cancer in a subject by administering an effective amount of a radioconjugated agent that targets one or more natural killer group 2, member D (NKG2D) ligands, alone or in combination with additional therapeutic agents or modalities. The radioconjugated NKG2DL-targeting agent targets NKG2DL-positive cells, such as tumor cells, depleting those cells and bystander NKG2DL-negative cells to effect overall tumor reduction. Moreover, radiation from the radioconjugated NKG2DL-targeting agent may increase expression of the target NKG2DL, leading to a feed-forward mechanism that further enhances the accumulation of the NKG2DL-targeting agent within the tumor.

Abstract: Provided are methods for treating a solid cancer in a subject by administering an effective amount of a radioconjugated CCR8-targeting agent to deplete tumor-associated CCR8-positive Treg cells, alone or in combination with one or more additional therapeutic agents or modalities, such as a radioconjugated CD33-targeting agent.