Using targeted radiotherapy (TRT) to drive anti-tumor immune response to immunotherapies

A method of treating a metastatic cancer in a subject, wherein the metastatic cancer comprises a primary malignant solid tumor and one or more metastatic tumors capable of causing concomitant immune tolerance, comprising systemically administering to the subject:

• (a) an immunomodulatory dose of a targeted radiotherapy (TRT) agent that is differentially taken up by and retained within the malignant solid tumor tissue, wherein the TRT agent is a phospholipid ether metal chelate or a radiohalogenated phospholipid ether that has the formula:
• or a salt thereof, wherein:
• R1 comprises (a) a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days;
• or (b) a radioactive halogen isotope;
• a is 0 or 1;
• Y is selected from the group consisting of —H, —OH, —COOH, —COOX, —OCOX, and —OX, wherein X is an alkyl or an arylalkyl;
• and wherein:
• (i) m is 0, b is 1, n is an integer from 12 to 30, and R2 is —N+Z3, wherein each Z is independently an alkyl or an aryl;
• or
• (ii) m is 1, b is 1, n is an integer from 12 to 30, and R2 is —N+Z3, wherein each Z is independently an alkyl or an aryl;
• or
• (iii) m is 0, b is 1, n is 18, and R2 is —N+Z3, wherein each Z is independently an alkyl or an aryl;
• or
• (iv) m is 1, b is 1, n is 18, and R2 is —N+Z3, wherein each Z is independently an alkyl or an aryl;
• and
• (b) one or more immunostimulatory agents capable of stimulating specific immune cells within the tumor microenvironment;
• whereby the concomitant immune tolerance caused by the metastatic tumors is prevented and the metastatic cancer is treated in the subject.