Methods and compositions for treating solid tumors and enhancing tumor vaccines

Patent metadata

Field	Value
Publication number	US-2016368996-A1
Application number	US-201615001241-A
Country	US
Kind code	A1
Filing date	Jan 20, 2016
Priority date	Mar 21, 2007
Publication date	Dec 22, 2016
Grant date	—

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.

First claim

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

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

3 . (canceled)

4 . The method of claim 1 , wherein said compound is an antisense compound or RNA inhibitory molecule.

5 . 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 activity or expression of an Endothelin B receptor (ETRB), thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.

6 . The method of claim 5 , wherein said compound is BQ788; Bosentan (Tracleer™); tezosentan, or an antibody.

7 . (canceled)

8 . The method of claim 5 , wherein said compound is an antisense compound or RNA inhibitory molecule.

9 . A method of treating or enhancing 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 expression or activity 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, thereby treating or enhancing efficacy of an immunotherapy for a solid tumor in a subject.

10 . The method of claim 9 , wherein said compound is an antisense compound or RNA inhibitory molecule.

11 . (canceled)

12 . (canceled)

13 . (canceled)

14 . The method of claim 2 , wherein said compound is an antibody.

15 . (canceled)

16 . (canceled)

17 . A method of treating or enhancing 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 expression or activity of a protein selected from 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, EIF5B, 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, thereby treating or enhancing efficacy of an immunotherapy for a solid tumor in a subject.

18 . The method of claim 17 , wherein said compound is an antisense compound or RNA inhibitory molecule.

19 . (canceled)

20 . (canceled)

21 . (canceled)

22 . The method of claim 19 , wherein said compound is an antibody.

23 . (canceled)

24 . (canceled)

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 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.

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

27 . (canceled)

28 . (canceled)

29 . A method of identifying a subject with a solid tumor likely to benefit from a chemotherapy prior to an oncologic surgery or likely to benefit from an immunotherapy, said method comprising the steps of
a. measuring an expression level of an Endothelin B receptor (ETRB) or a nucleotide molecule encoding an Endothelin B receptor (ETRB) in said solid tumor; and b. comparing said expression level to a reference standard, whereby, if said expression level is higher than said reference standard, then said subject is likely to benefit from said chemotherapy prior to said oncologic surgery or likely to benefit from said immunotherapy.

30 . (canceled)

31 . (canceled)

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.

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

Assignees

• Univ Pennsylvania

Inventors

• Buckanovich Ronald J
• Coukos George
• Facciabene Andrea

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• G01N2333/70525

  ICAM molecules, e.g. CD50, CD54, CD102 · CPC title