Methods and compositions for treating solid tumors and enhancing tumor vaccines

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.

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). 
     
     
         2 . The method of  claim 1 , wherein said compound is BQ788; Bosentan (Tracleer™); tezosentan, or an antibody. 
     
     
         3 .- 12 . (canceled) 
     
     
         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. 
     
     
         14 . The method of  claim 13 , wherein said compound is an antibody. 
     
     
         15 .- 20 . (canceled) 
     
     
         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. 
     
     
         22 . The method of  claim 21 , 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 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. 
     
     
         26 . The method of  claim 25 , wherein said compound is an antisense compound or RNA inhibitory molecule or an antibody. 
     
     
         27 .- 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.