Methods and compositions for treating cancer with cancer-binding adjuvants

Patent metadata

Field	Value
Publication number	US-2026053935-A1
Application number	US-202319103723-A
Country	US
Kind code	A1
Filing date	Aug 17, 2023
Priority date	Aug 18, 2022
Publication date	Feb 26, 2026
Grant date	—

Abstract

Disclosed herein are compositions comprising immune-activating agents that bind the tumor cell surface in the absence of a tumor-targeting protein component. Described herein are methods and compositions for targeting a TLR or STING agonist to tumor cells and/or cells in the tumor microenvironment. It is hypothesized that the metabolic stress of tumor growth also produces an excess of unpaired cysteines on cell surface proteins relative to the rest of the body. Therefore, this chemistry can be used with compounds that would preferentially target unpaired cysteines on cell surface proteins.

First claim

1 . A polymer comprising the structure (I):

W, Y, and X are each independently a monomer unit of a polymer;
A comprises a group that binds to an Antigen Presenting Cell (APC) mannose receptor;
Z comprises a TLR or STING agonist;
B comprises a pyridyl disulfide moiety or a maleimide moiety;
m is an integer ranging from 0 to 150;
p is an integer ranging from 0 to 10; and
b is an integer ranging from 1 to 10.

2 . The polymer of claim 1 , wherein W, Y, and X are each independently polymerized monomer units of polyacrylate, a polyacrylamide, a saturated polyolefin, a polyamide, a peptide, a polypeptide, an unsaturated olefin formed by ring opening metathesis polymerization, a siloxane, a polysiloxane, a polyether, a polysaccharide, a polyoxazoline, a polyimine, a polyvinyl derivative or any combination thereof.

3 . The polymer of claim 1 or 2 , where W, Y, and X are independently selected from acrylic acid, methacrylic acid, acrylamide, methacrylamide, N-(2-hydroxypropyl) methacrylamide, N-(2-hydroxyethyl) methacrylamide, natural and un-natural amino acids, silanols, monosaccharides, glycols, substituted and unsubstituted 2-oxazolines N-substituted and unsubstituted aziridine, substituted and unsubstituted 2-ethyl-2-oxazoline.

4 . The polymer of any one of claims 1-3 , wherein the TLR agonist has the general structure (II),

wherein R 1 and R 2 are each independently a hydrogen atom, a halogen, an alkyl group, a substituted alkyl group, a heteroalkyl group, a substituted heteroalkyl group, a cycloalkyl group, a substituted cycloalkyl group, a heterocycloalkyl group, a substituted heterocycloalkyl group, an aryl group, a substituted aryl group, a heteroaryl group, a substituted heteroaryl group, an alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, and alkoxyalkoxyalkyl group, an amino group, or a hydroxyl group.

5 . The polymer of any one of claims 1-4 , wherein moiety

is further defined as

wherein L′ is a substituted or unsubstituted alkyl group comprising from 1 to 9 carbon atoms, a substituted or unsubstituted alkyl group comprising from 1 to 9 carbon atoms, or an ethylene glycol moiety comprising from 1 to 9 ethylene glycol groups.

6 . The polymer of any one of claims 1-5 , wherein Z is selected from:

7 . The polymer of any one of claims 1-6 , wherein

8 . The polymer of any one of claims 1-7 , wherein

9 . The polymer of any one of claims 1-7 , wherein

wherein q is 2 to 9.

10 . The polymer of any one of claims 1-9 , wherein moiety

is further defined as

11 . The polymer of any one of claims 1-9 , wherein moiety

is further defined as

12 . The polymer of any one of claims 1-11 , wherein moiety

is further defined as

13 . The polymer of any one of claims 1-12 , wherein moiety

is further defined as

14 . The polymer of any one of claims 1-13 , wherein moiety

is further defined as

15 . The polymer of any one of claims 1-14 , wherein moiety

is further defined as

16 . The polymer of any one of claims 1-15 , wherein moiety

is further defined as

wherein R 1 and R 2 are each independently a hydrogen atom, a halogen, an alkyl group, a substituted alkyl group, a heteroalkyl group, a substituted heteroalkyl group, a cycloalkyl group, a substituted cycloalkyl group, a heterocycloalkyl group, a substituted heterocycloalkyl group, an aryl group, a substituted aryl group, a heteroaryl group, a substituted heteroaryl group, an alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, and alkoxyalkoxyalkyl group, an amino group, or a hydroxyl group.

17 . The polymer of any one of claims 1-16 , wherein moiety

is further defined as

18 . The polymer of any one of claims 1-17 , wherein the polymer comprises at least one TLR or STING agonist and at least one group that binds to an Antigen Presenting Cell (APC) mannose receptor.

19 . The polymer of any one of claims 1-18 , wherein the polymer is further defined as

wherein E and Q are end units and each independently comprises a residue of the polymer, a fluorescent molecule, an albumin polypeptide, a dithioate group, an azide, a linker, an immunomodulating agent, a pyridyl disulfide moiety, a maleimide moiety, a TLR agonist, a STING agonist, a group that binds to an Antigen Presenting Cell (APC) mannose receptor, or combinations thereof.

20 . The polymer of claim 19 , wherein the dithioate group is further defined as

wherein R is an alkyl or aryl group containing from 1 to 12 carbon atoms.

21 . The polymer of claim 19 , wherein the linker comprises a polyethylene glycol moiety or a hydrocarbon moiety.

22 . The polymer of claim 21 , wherein the polyethylene glycol linker compr

Assignees

• Univ Chicago

Inventors

• Hubbell Jeffrey A
• Slezak Anna J
• Bennish Levi Y
• Battistella Claudia

Classifications

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C08L33/24

  Homopolymers or copolymers of amides or imides · CPC title