Methods of diagnosing cancer using cancer testis antigens
AssigneeYissum Research Development Company of the Hebrew University of Jerusalem
InventorYoav SMITH
Life of this patent
Estimating the term…
Abstract
Methods and kits for the diagnosis of cancer based on specific expression profiles of Cancer Testis Antigens (CTA) are provided.
Claims36
A method for determining a cancer testis antigen (CTA) signature in a non-testis biological sample, the method comprises the steps of:
- (a) determining an expression profile of a plurality of antigens selected from the group consisting of:
- CEP55, GAGE8/GAGE12F, ZNF165, PRAME, SPAG4, PAGE4, PBK, SPANXA2/B1/C/A1, TSPY8/4/3/1, and GAGE12D/12F, in the non-testis biological sample obtained from the subject;
- and
- (b) comparing the expression profile to a reference expression profile, thereby determining the CTA signature in the non-testis biological sample.
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A method for diagnosing, prognosticating, monitoring or determining severity of cancer in a subject, the method comprises the steps of:
- (a) determining an expression profile of a plurality of antigens listed in Table 2, in a non-testis biological sample obtained from a subject;
- and
- (b) comparing said expression profile to a reference expression profile, wherein:
- (i) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- RBM46, CT47A1/A2/A3/A4/A5/A6/A8/A9/A10/A7/A11, PBK, DDX53, MAGEB3, LOC653786/OTOA, DMRT1, LDHC, CCDC83, ANKRD45, DDX53, BAGE, TDRD1, CEP55, PRM1, SSX2B/2, SEMG1, and TPTE, compared to said reference is indicative of breast cancer,
- (ii) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- MAGEB4, TTK, CEP55, SLCO6A1, PBK, SPA17, ATAD2, FAM133A, TTK, MAGEA1, OIP5, CABYR, SSX1, MAGEA3, SSX2B/2, MAGEA6, MAGEA12, CTNNA2, TPTE, SSX4B/4, XAGE1B/1E, MAGEC1, GAGE8/12F/2A/2D/12J/12G/2B/2E/12I/7/6/E5/4/3/2C/1, GAGE12D/12F/2A/12H/12E/12C/12G/12I/7/6/5/4/2C, and GAGE12F/12G/12I/7/5 is indicative of liver cancer,
- (iii) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- FAM133A, MORC1, TEX14, ANKRD45, MAGEB2, MAGEC1 and ELOVL4, is indicative of multiple myeloma,
- (iv) an increase in expression of an expression profile of a plurality of antigens selected from:
- IL13RA2, ZNF165, CEP55, CTAG2, SPAG4, MORC1 and SPAG8, is indicative of glioblastoma,
- (v) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- MAGEA1 1, ODF2, IL13RA2, MAGEA6, DDX43, CEP55, MAGEA1, MAGEB3, SPANXB1, BAGE, TSGA10, MAGEA3, MAGEA12, MAGEA1, and IL13RA2, is indicative of colon cancer,
- (vi) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- PBK, MAGEA12, SPAG4, ELOVL4, CEP55, TTK, ATAD2, OIP5, FAM133A, FATE1, IL13RA2, PRAME, MAGEA6, CTNNA2, MAGEA3, PLAC1, is indicative of adrenal cancer,
- (vii) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- PRAME, CTNNA2, MAGEA2B/2, TMEFF1, IGSF11, MAGEA3, SSX1, MAGEA6, MAGEA12, PBK, ANKRD45, SSX4B/4, MAGEC1, SSX2B/2, MAGEA1, MAGEC2, DSCR8, TTK, CTAG1A/B, TPTE, XAGE1B/1E and IL13RA2, is indicative of melanoma cancer,
- (viii) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- ZNF165, PRAME, GAGE1, GAGE12F/G/I/7/5, SPAG1, TTK, LEMD1, SPA17, PBK, TMEFF1, CEP55, CTNNA2, SPAG4, CTCFL, SPAG17, BAGE, ATAD2, PRSS54, GPAT2, CCDC83, MAGEA11, CT45A2/A1/A6/A5/A4/A3, LY6K, TSGA10, DSCR8, CTAG1A/CTAG1B, and SAGE1 is indicative of ovarian cancer,
- (ix) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- TDRD1, POTED, DCAF12 and TSGA10 is indicative of prostate cancer, and
- (x) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- CEP55, GAGES/12F, SPAG4, LOC653786/OTOA, CTNNA2, TPTE, ATAD2, GAGE8/12F/2A/2D/12J/12G/2B/2E/121/7/6/5/4/3/2C/1, MAGEA6, MORC1, TTK, PBK, RGS22, TMEFF1, ARX, MAGEB4, PRAME, GAGE12D/2F/2A/12H/12E/12C/12G/121/7/6/5/4/2C, TEX14, POTED, DMRT1, CTCFL, GPAT2, GAGE12F/12G/2I/E7/E5, GAGE3, SPANXA2/C/A1, DDX43, and GAGE1, is indicative of kidney cancer;
- (xi) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- DDX43, SSX1, ATAD2 and CEP55 is indicative of uveal melanoma;
- (i) an increase in expression of an expression profile of a plurality of antigens selected from the group consisting of:
- LY6K, MAGEA6, PLAC1, LEMD1, MAGEA1, MAGEA11, MAGEA4, MAGEA12, and CEP55 is indicative of oral squamous cell carcinoma;
- thereby determining a cancerous state in said subject.
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The method of claim , wherein said reference expression profile is obtained from one or more control biological samples selected from the group consisting of:
- a sample from at least one healthy subject, a panel of samples from healthy subjects, and a stored set of data from healthy subjects.
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A method for diagnosing, prognosticating, monitoring or determining severity of cancer in a subject, the method comprises the steps of:
- (a) obtaining a comparison determining an expression profile of a plurality of CT antigens selected from:
- ZNF165, GAGE1, PRAME, GAGE12, PBK, XAGE1B, IL13RA2, MORC1, BAGE2, CEP55, SPAG4, CTNNA2, GAGE8, OTOA, RBM46, DDX53, CT47A1, TDRD1, DCAF12, POTED, TSGA10, MAGEB4, TTK, SLCO6A1, FAM133A, ANKRD45, ELOVL4, MAGEB2, TEX14, MAGEC1, and MAGEA12, in a non-testis biological sample obtained from a subject;
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- (b) comparing said expression profile to a reference expression profile of said CT antigens, wherein:
- (i) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- ZNF165, GAGE1, PRAME, and GAGE12, compared to said reference is indicative of ovarian cancer,
- (ii) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- PBK, XAGE1B, IL13RA2, MORC1, and BAGE2, compared to said reference is indicative of lung cancer,
- (iii) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- CEP55, SPAG4, CTNNA2, GAGES, and OTOA, compared to said reference is indicative of kidney cancer,
- (iv) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- RBM46, DDX53, and CT47A1, compared to said reference is indicative of breast cancer,
- (v) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- TDRD1, DCAF12, POTED, and TSGA10, compared to said reference is indicative of prostate cancer,
- (vi) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- MAGEB4, TTK, and SLCO6A1, compared to said reference is indicative of liver cancer,
- (vii) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- PRAME and CTNNA2, compared to said reference is indicative of melanoma,
- (viii) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- FAM133A, ANKRD45, ELOVL4, MORC1, MAGEB2, TEX14, MAGEC1, compared to said reference is indicative of multiple myeloma,
- (ix) an increase in expression of an expression profile of a plurality of CTAs selected from the group consisting of:
- LY6K, MAGEA6, PLAC1, LEMD1, MAGEA1, MAGEA11, MAGEA4, MAGEA12, and CEP55 is indicative of oral squamous cell carcinoma,
- (x) an increase in expression of an expression profile of a plurality of CTAs selected from the group consisting of:
- TTK and PRAME, compared to said reference is indicative of lung cancer, and
- (xi) an increase in expression of an expression profile of a plurality of CT antigens selected from the group consisting of:
- PBK, SPAG4, MAGEA12, and ELOVL4, compared to said reference is indicative of adrenal carcinoma.
A kit comprising reagents adapted to specifically determine the expression level of a plurality of antigens selected from the group consisting of:
- (i) a plurality of CTAs selected from the group consisting of:
- CEP55, GAGE8/GAGE12F, ZNF165, PRAME, SPAG4, PAGE4, PBK, SPANXA2/B1/C/A1, TSPY8/4/3/1, and GAGE12D/12F;
- (ii) a plurality of CTAs selected from the group consisting of:
- RBM46, CT47A1/A2/A3/A4/A5/A6/A8/A9/A10/A7/A11, PBK, DDX53, MAGEB3, LOC653786/OTOA, DMRT1, LDHC, CCDC83, ANKRD45, DDX53, BAGE, TDRD1, CEP55, PRM1, SSX2B/2, SEMG1, TPTE and SPAG1;
- (iii) a plurality of CTAs selected from the group consisting of:
- MAGEB4, TTK, CEP55, SLCO6A1, PBK, SPA17, ATAD2, FAM133A, TTK, MAGEA1, OIP5, CABYR, SSX1, MAGEA3, SSX2B/2, MAGEA6, MAGEA12, CTNNA2, TPTE, SSX4B/4, XAGE1B/1E, MAGEC1, GAGE8/12F/2A/2D/12J/12G/2B/2E/121/7/6/E5/4/3/2C/1, GAGE12D/12F/2A/12H/12E/12C/12G/121/7/6/5/4/2C, and GAGE12F/12G/121/7/5;
- (iv) a plurality of CTAs selected from the group consisting of:
- FAM133A, MORC1, TEX14, ANKRD45, MAGEB2, MAGEC1 and ELOVL4;
- (v) a plurality of CTAs selected from the group consisting of:
- MAGEA11, ODF2, IL13RA2, MAGEA6, DDX43, CEP55, MAGEA1, MAGEB3, SPANXB1, BAGE, TSGA10, MAGEA3, MAGEA12, MAGEA1, and IL13RA2;
- (vi) a plurality of antigens selected from the group consisting of:
- CEP55, TTK, ATAD2, OIP5, FAM133A, FATE1, IL13RA2, PRAME, MAGEA6, CTNNA2, MAGEA3, PLAC1, PBK, MAGEA12, SPAG4 and ELOVL4,
- (vii) a plurality of CTAs selected from the group consisting of:
- PRAME, CTNNA2, MAGEA2B/MAGEA2, TMEFF1, IGSF11, MAGEA3, SSX1, MAGEA6, MAGEA12, PBK, ANKRD45, SSX4B/SSX4, MAGEC1, SSX2B/SSX2, MAGEA1, MAGEC2, DSCR8, TTK, CTAG1A/CTAG1B, TPTE, XAGE1B/XAGE1E and IL13RA2, and
- (viii) a plurality of CTAs selected from the group consisting of:
- ZNF165, PRAME, GAGE1, GAGE12F/G/I/7/5, SPAG1, TTK, LEMD1, SPA17, PBK, TMEFF1, CEP55, CTNNA2, SPAG4, CTCFL, SPAG17, BAGE, ATAD2, PRSS54, GPAT2, CCDC83, MAGEA11, CT45A2/A1/A6/A5/A4/A3, LY6K, TSGA10, DSCR8, CTAG1A/CTAG1B, and SAGE1;
- (ix) a plurality of CTAs selected from the group consisting of:
- TDRD1, POTED, DCAF12 and TSGA10,
- (x) a plurality of CTAs selected from the group consisting of:
- CEP55, GAGES/12F, SPAG4, LOC653786/OTOA, CTNNA2, TPTE, ATAD2, GAGE8/12F/2A/2D/12J/12G/2B/2E/121/7/6/5/4/3/2C/1, MAGEA6, MORC1, TTK, PBK, RGS22, TMEFF1, ARX, MAGEB4, PRAME, GAGE12D/2F/2A/12H/12E/12C/12G/121/7/6/5/4/2C, TEX14, POTED, DMRT1, CTCFL, GPAT2, GAGE12F/12G/2I/E7/E5, GAGE3, SPANXA2/C/A1, DDX43, and GAGE1;
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- (xi) a plurality of CTAs selected from the group consisting of:
- DDX43, SSX1, ATAD2 and CEP55.
A kit comprising reagents adapted to specifically determine the expression level of a plurality of antigens selected from the group consisting of:
- (i) a plurality of CTAs selected from the group consisting of:
- ZNF165, GAGE1, PRAME, and GAGE12,
- (ii) a plurality of CTAs selected from the group consisting of:
- PBK, XAGE1B, IL13RA2, MORC1, and BAGE2,
- (iii) a plurality of CTAs selected from the group consisting of:
- CEP55, SPAG4, CTNNA2, GAGES, and OTOA,
- (iv) a plurality of CTAs selected from the group consisting of:
- RBM46, DDX53, and CT47A1,
- (v) a plurality of CTAs selected from the group consisting of:
- TDRD1, DCAF12, POTED, and TSGA10,
- (vi) a plurality of CTAs selected from the group consisting of:
- MAGEB4, TTK, and SLCO6A1,
- (vii) a plurality of CTAs selected from the group consisting of:
- PRAMS and CTNNA2,
- (viii) a plurality of CTAs selected from the group consisting of:
- FAM133A, ANKRD45, ELOVL4, MORC 1, MAGEB2, TEX14, MAGEC 1,
- (ix) a plurality of CTAs selected from the group consisting of:
- TTK and PRAME,
- (x) a plurality of CTAs selected from the group consisting of:
- PBK, SPAG4, MAGEA12, and ELOVL4,
- (xi) a plurality of CTAs residing on a non-X chromosome selected from the group consisting of:
- CEP55, TTK, ATAD2 and OIP5, and a plurality of antigens selected from the group consisting of:
- FOXM1, UBE2C, MAD2L1, CCNB2, CDC20, CKS2, RRM2 CCNB1, AURKB, ECT2, and NEK2,
- (xii) a plurality of CTAs residing on a non-X chromosome selected from the group consisting of:
- CEP55, PBK and TTK, and a plurality of CTAs residing on the X chromosome selected from the group consisting of:
- MAGE, GAGE, and SPANX
- (xiii) a plurality of CTAs selected from the group consisting of:
- LY6K, MAGEA6, PLAC1, LEMD1, MAGEA1, MAGEA11, MAGEA4, MAGEA12, and CEP55 in indicative of oral squamous cell carcinoma.
Dependencies are inferred from the claim text.