Abstract: Methods for treating cancers and precancerous conditions by administering an effective amount of a radiolabeled agent that targets cell surface phosphatidylserine, alone or in combination with other therapies, are provided. The radiolabeled phosphatidylserine targeting agent delivers radiation to cells that externally present phosphatidylserine, such as tumor cells, depleting those cells and neighboring malignant cells to effect overall tumor reduction. Radiation delivered by the radiolabeled phosphatidylserine targeting agent itself increases the cell surface expression of phosphatidylserine, leading to a feed-forward mechanism that drives further accumulation of the phosphatidylserine targeting agent at target lesions to enhance its therapeutic effect.

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.