US 12,109,256 B2
Radiohalogenated agents for in situ immune modulated cancer vaccination
Jamey Weichert, Sun Prairie, WI (US); Paul M. Sondel, Madison, WI (US); Anatoly Pinchuk, Fitchburg, WI (US); Zachary Morris, Madison, WI (US); Mario Otto, Fitchburg, WI (US); and Bryan Bednarz, Madison, WI (US)
Assigned to Wisconsin Alumni Research Foundation, Madison, WI (US)
Filed by Wisconsin Alumni Research Foundation, Madison, WI (US)
Filed on Jul. 2, 2020, as Appl. No. 16/919,191.
Application 16/919,191 is a continuation of application No. 15/652,400, filed on Jul. 18, 2017, granted, now 10,736,949.
Claims priority of provisional application 62/363,608, filed on Jul. 18, 2016.
Prior Publication US 2020/0330567 A1, Oct. 22, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61K 39/39 (2006.01); A61K 39/395 (2006.01); A61K 51/04 (2006.01)
CPC A61K 39/001 (2013.01) [A61K 39/0011 (2013.01); A61K 39/39 (2013.01); A61K 39/39558 (2013.01); A61K 51/0408 (2013.01); A61K 51/041 (2013.01); A61K 51/0489 (2013.01); A61K 2039/505 (2013.01); A61K 2039/53 (2013.01); A61K 2039/545 (2013.01); A61K 2039/55511 (2013.01); A61K 2039/55533 (2013.01); A61K 2039/572 (2013.01); A61K 2039/58 (2013.01); A61K 2039/585 (2013.01)] 18 Claims
 
1. 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, the method comprising the steps of:
(a) administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue and comprises a metaiodobenzylguanidine (MIBG), wherein the iodine atom in the MIBG is a radioactive iodine isotope, or a phospholipid compound having the formula:

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R1 comprises a radioactive halogen isotope;
a is 0 or 1;
n is an integer from 12 to 30;
m is 0 or 1;
Y is selected from the group consisting of —H, —OH, —COOH, —COOX, —OX, and —OCOX, wherein X is an alkyl or an arylalkyl; and
R2 is selected from the group consisting of —N+H3, —N+H2Z, —N+HZ2, and —N+Z3, wherein each Z is independently an alkyl or an aryl; and
(b) performing in situ tumor vaccination in the subject at the primary malignant solid tumor using one or more treatments capable of stimulating specific immune cells within the tumor microenvironment, wherein the one or more treatments capable of stimulating specific immune cells within the tumor microenvironment comprise contacting the primary malignant solid tumor with a composition comprising one or more 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.