Methods and compositions for treating solid tumors and enhancing tumor vaccines
AssigneeUniversity of Pennsylvania
InventorsRonald J. Buckanovich, George Coukos, Andrea Facciabene
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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.
Claims33
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 an activity of an Endothelin B receptor (ETRB), thereby treating a solid tumor in a subject.
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 an expression of an Endothelin B receptor (ETRB), thereby treating a solid tumor in a subject.
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 activity of an Endothelin B receptor (ETRB), thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
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 of an Endothelin B receptor (ETRB), thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
A method of treating a solid tumor in a subject, comprising the step of contacting said subject with a compound or composition that reduces an 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, SLC 1A4, and SGCB, thereby treating a solid tumor in a subject.
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 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, MPHOSPH9, IMAGE:1660792, IMAGE:191524, IMAGE:2365035, TAF3, SLC1A4, and SGCB, thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
A method of treating a solid tumor in a subject, comprising the step of contacting said subject with a compound or composition that reduces an 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, SLCIA4, and SGCB.
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 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, MPHOSPH9, IMAGE:1660792, IMAGE:191524, IMAGE:2365035, TAF3, SLC1A4, and SGCB, thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
A method of treating a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that increases an expression 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 a solid tumor in a subject.
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 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 enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
A method of treating a solid tumor in a subject, comprising the step of contacting said subject with a compound or a composition that increases an activity 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, 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 a solid tumor in a subject.
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 composition that increases an activity 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, 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 enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
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, thereby enhancing an efficacy of an immunotherapy for a solid tumor in a subject.
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 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.
A method of identifying a subject with a solid tumor likely to benefit from a chemotherapy prior to an oncologic surgery, 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.
A method of prognosticating a solid tumor in a subject, 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 prognosis is less favorable than a subject for whom said expression level is lower than or equal to said reference standard.
A method of identifying a subject with a solid tumor 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 lower than said reference standard, then said subject is likely to benefit from an immunotherapy.
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.
Dependencies are inferred from the claim text.