# US 2019/0375845 A1 · Methods and compositions for treating solid tumors and enhancing tumor vaccines

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0375845 A1
- Document ID: US20190375845A1
- Status: Published application
- Kind: A1
- Application number: 16/241,676
- Filed: 2019-01-07
- Published: 2019-12-12
- Earliest claimed: 2007-03-21
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Ronald J BUCKANOVICH; George COUKOS; Andrea FACCIABENE
- Web page: https://patentgrep.com/patent/US20190375845A1

## CPC

- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 38/06: Tripeptides
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- C12N 15/1138: {against receptors or cell surface proteins}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/30: Special therapeutic applications
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 2333/70525: ICAM molecules, e.g. CD50, CD54, CD102
- G01N 2333/726: G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention provides methods of treating and enhancing efficacy of immunotherapy for a solid tumor in a subject, comprising the step of contacting the subject with a compound or composition that modulates the expression or activity of ETRB, ET-1, ICAM-1, or another protein found herein to play a role in homing of T cells to a solid tumor. The present invention also provides methods of prognosticating a solid tumor in a subject, comprising the step of measuring an expression level of a protein found herein to play a role in homing of T cells to a solid tumor, or a nucleotide molecule encoding same.

## Claims

### Claim 1

A method of treating or of enhancing an efficacy of an immunotherapy for a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that reduces an activity of or expression of an Endothelin B receptor (ETRB).

### Claim 2 (depends on 1)

The method of claim 1, wherein said compound is BQ788; Bosentan (Tracleer™); tezosentan, or an antibody.

### Claim at position 3

-12. (canceled)

### Claim 13

A method of treating or of enhancing an efficacy of an immunotherapy for a solid tumor in a subject, comprising the step of contacting said subject with a compound or composition that reduces an activity of or expression of a protein selected from Musashi 2, delta-like 1, Hairy/Enhancer of Split 1, MEG3, SEC61G, KIAA1609, ACTR6, clone LNG00414, ATP9A, IMAGE:23539, NCOA1, WIT1, PAPSS2, ALDOA, ZNF423, ENPP2, HSU79266, KIAA0146, IMAGE:1902075, EMX2, MYBL1, IMAGE:1660792, IMAGE:191524, IMAGE:2365035, TAF3, SLC1A4, and SGCB.

### Claim 14 (depends on 13)

The method of claim 13, wherein said compound is an antibody.

### Claim at position 6

-20. (canceled)

### Claim 21

A method of treating or of enhancing an efficacy of an immunotherapy for a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that increases an activity of or expression of a protein selected from a CASP8 and FADD-like apoptosis regulator (CFLAR) protein; estrogen receptor alpha (ESR1); caldesmin-1; adrenergic receptor B2 (ADRBK2); IMAGE:2755380, ZNFN1A5, LOC283663, IGLJ3, ZNF521, COL05405, CYP1B1, EIFSB, IMAGE:1518332, HSPC056, FLJ32949, IMAGE:244300, FLJ10330, C18orf14, IMAGE:2115041, GBP1, IMAGE:731714, SFRS1, NICAL, NOL7, MYCBP2, IMAGE:2275600, ADRBK2, EST366269, SCAP2, STK3, and AKAP10.

### Claim 22 (depends on 21)

The method of claim 21, wherein said compound is an antibody.

### Claim 23

(canceled)

### Claim 24

(canceled)

### Claim 25

A method of enhancing an efficacy of an immunotherapy for a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that reduces an expression or activity of an endothelin-1 (ET-1) protein or that reduces interaction between an Endothelin B receptor (ETRB) and an endothelin-1 (ET-1), thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.

### Claim 26 (depends on 25)

The method of claim 25, wherein said compound is an antisense compound or RNA inhibitory molecule or an antibody.

### Claim at position 13

-31. (canceled)

### Claim 32

A method of enhancing an efficacy of an immunotherapy for a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that increases an expression or an activity of an intercellular adhesion molecule 1 (ICAM-1 protein), thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.

### Claim 33 (depends on 32)

The method of claim 32, wherein said compound is an antisense compound, RNA inhibitory molecule, or an antibody.