Title: Ctage gene family
United States Patent: 7,314,922
Issued: January 1, 2008
Stefan (Edingen-Neckarhausen, DE), Schadendorf; Dirk (Mannheim, DE),
Usener; Dirk (Mainz, DE)
Krebsforschungszentrum (Heidelberg, DE)
Appl. No.: 10/110,807
Filed: October 13, 2000
PCT Filed: October 13, 2000
PCT No.: PCT/DE00/03628
September 06, 2002
PCT Pub. No.: WO01/27255
PCT Pub. Date: April 19,
Executive MBA in Pharmaceutical Management, U. Colorado
The present invention relates to a novel
gene family for "cutaneous T-cell lymphoma associated genes" (CTAGE). The
present invention describes two members of said family, CTAGE-1 and
CTAGE-2, the underlying genes thereof and the use thereof for diagnosis
and treatment of tumoral diseases.
Description of the
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is filed under the provisions of 35 U.S.C. .sctn.371 and
claims the priority of International Patent Application No. PCT/DE00/03628
filed Oct. 13, 2000, which in turn claims priority of German Patent
Application No. 199 49 595.5 filed Oct. 14, 1999.
FIELD OF THE INVENTION
The present invention relates to a novel gene family for "cutaneous T-cell
lymphoma associated genes" (CTAGE). The present invention describes two
members of this family, CTAGE-1 and CTAGE-2, the underlying cDNA thereof
(ctage-1 and ctage-2), and the use thereof for diagnosis and therapy of
1. Background of the Invention
The cutaneous T-cell lymphoma (CTCL) is a tumor of the skin which is based
on T-lymphocytes and difficult to treat in an advanced stage. The
cutaneous T-cell lymphomas are generally counted among the group of
non-Hodgkin's lymphomas. The cutaneous T-cell lymphomas comprise inter
alia the diseases mycosis fungoides, Sezary syndrome and pagetoid
reticulosis. After removing the primary tumor, conventional therapies
(irradiation, chemotherapy) often have only little effectiveness in the
metastasizing stage of the disease or as a preventive therapy and are also
accompanied by the known major side-effects. The tumor has often grown and
spread to such an extent that operative treatment is of no use. The
measure of a possible immunotherapy (vaccination against tumors) has
recently been considered in particular for tumors of the skin. However,
the application of such therapy forms requires tumor-specific antigens
which have not been found for many tumor types thus far.
2. Description of the Invention
Thus, the invention is substantially based on the problem of discovering
tumor-specific antigens which are suited inter alia for cutaneous T-cell
lymphomas and can be used for a vaccination therapy.
The solution to this technical problem was obtained by providing the
embodiments characterized in the claims.
The inventors were able to isolate a DNA molecule family which in addition
to expression in testis tissues is only expressed in different tumor
tissues, in particular in the case of T-cell lymphomas (such as the Sezary
syndrome), tumors of the HNO region or ovarian cancers (see Examples 4 and
5). They belong to what is called "cancer-testis antigens". The
identification of such genes (CTAGE-1 and CTAGE-2) is of interest, since
the proteins encoded by them and peptides derived therefrom serve as
target structures, e.g. for cytotoxic cells, and can be used as antigens
for the production of diagnostic or therapeutic antibodies. For tumor
therapy, the peptides encoded by CTAGE-1 or CTAGE-2 or fragments thereof
can be either applied directly or loaded on antigen-presenting cells.
Peptides presenting the antigens can also be expressed by means of vectors
in different cells (e.g. dendritic cells as antigen-presenting cells).
Furthermore, cloning of one or more representatives of the CTAGE gene
family forms the foundation for developing diagnostic tests to ensure a
more reliable and early diagnosis in affected persons in the future.
Functional analyses of the protein will no doubt add to the insight into
the development of tumors. Thus, they have to be regarded as candidate
genes for studying the pathomechanisms on which different tumoral diseases
The present invention therefore relates to a DNA molecule coding for a
tumor-associated antigen, comprising: (a) the nucleic acid of FIG. 1 (SEQ
ID NO: 1, see Original
Patent) or FIG. 2 (SEQ ID NO: 4, see Original
Patent) or a DNA differing therefrom by one or more base pairs or a
fragment thereof, (b) a DNA hybridizing with the nucleic acid from (a), or
(c) a DNA related to the nucleic acid from (a) or (b) via the degenerated
The nucleic acid molecules defined in items (a) and (c) code for proteins,
polypeptides or peptides, which still have at least one of the below
described biological activities of the protein encoded by the nucleic acid
according to FIG. 1 or FIG. 2, e.g. represent a tumor-specific antigen.
The DNA molecules defined in (a) also comprise DNA molecules differing
from the sequence indicated in FIGS. 1 and/or 2 by deletion(s),
insertion(s), substitution(s) and/or other modifications known in the art,
e.g. alternative splicing, or comprise a fragment of the original nucleic
acid molecule, the protein encoded by these DNA molecules additionally
having one or more of the above described biological activities. Allele
variants are also counted thereamong. Methods of producing the above
modifications in the nucleic acid sequence are known to a person skilled
in the art and are described in standard manuals of molecular biology,
e.g. in Sambrook et al., Molecular Cloning: A Laboratory Manual, 2.sup.nd
edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor N.Y.
(1989). In this connection, the variants have a homology of at least 70%,
preferably 80%, more preferably 90%, and most preferably 95, 96, 97, 98 or
99%, with the sequences according to FIG. 1 or 2.
The term "hybridizing DNA" refers to a DNA which hybridizes under common
conditions, in particular at 20.degree. C. below the melting point of the
DNA, with a DNA from (a) In this connection, the term "hybridize" refers
to conventional hybridization conditions, preferably to hybridization
conditions in which 5.times.SSPE, 1% SDS, 1.times. Denhardt's solution is
used as the solution and the hybridization temperatures are between
35.degree. C. and 70.degree. C., preferably at 65.degree. C. Following
hybridization, it is preferred to first carry out a wash step with
2.times.SSC, 1% SDS and then with 0.2.times.SSC at temperatures between
35.degree. C. and 70.degree. C., preferably at 65.degree. C. (for the
definitions of SSPE, SSC and Denhardt's solution see Sambrook et al.,
supra). Stringent hybridization conditions as described in Sambrook et
al., supra, for example, are preferred.
In a particularly preferred embodiment the DNA molecule according to the
invention is a cDNA.
In another preferred embodiment, the DNA molecule according to the
invention is a genomic DNA which is derived preferably from a mammal, e.g.
a human being. Screening methods based on nucleic acid hybridization
enable the isolation of the genomic DNA molecules according to the
invention from any organism or derived genomic DNA libraries, probes being
used which contain the nucleic acid sequence indicated in FIG. 1 or 2 or a
A nucleic acid according to the invention is particularly suited as an
antigen-coding structure for therapeutic purposes. Here, the objective is
to stimulate the immune system and/or eliminate tumor cells identified via
a member of the CTAGE family, particularly CTAGE-1 or CTAGE-2. There are
various possibilities to do so, e.g. giving the patient the naked DNA by
way of injection. For this purpose, a plasmid having a very active
promoter and a member of the CTAGE family, in particular CTAGE-1 or
CTAGE-2, are given by intramuscular or intradermal injection, for example.
What is aimed at is that the cells take up the plasmid, produce antigens,
present individual peptides via HLA molecules and thus evoke a cytotoxic
T-cell immunoresponse which shall then serve for warding off tumor cells.
This procedure is described generally in Conry et al., Clinical Cancer
Research, Vol. 4, pages 2903-2912 (1998). The gene-gun method is an
alternative. It is described in Fynan et al., Proc. Natl. Acad. Sci,
U.S.A., Vol. 90, pages 11478-11482 (1993).
The nucleic acids according to the invention can also be inserted in a
vector or expression vector. Hence the present invention also comprises
vectors containing the nucleic acid molecules. Examples thereof are known
to the person skilled in the art. In the case of an expression vector for
E. coli these are pGEMEX, pUC derivatives (e.g. pUC8), pBR322, pBLueScript,
pGEX-2T, pET3b and pQE-8, for example. For expression in yeast e.g. pY100
and Ycpad1 have to be mentioned while e.g. pKCR, pEFBOS, cDM8 and pCEV4
have to be indicated for expression in animal cells. The baculovirus
expression vector pAcSGHisNT-A is particularly suited for expression in
insect cells. In a preferred embodiment the nucleic acid molecule
according to the invention is functionally linked in the vector with
regulatory elements which enable the expression thereof in prokaryotic or
eukaryotic host cells. Along with the regulatory elements, e.g. a
promoter, such vectors contain typically a replication origin and specific
genes which enable the phenotypic selection of a transformed host cell.
The regulatory elements for expression in prokaryotes, e.g. E. coli,
comprise the lac-, trp promoter or T7 promoter, and those for expression
in eukaryotes comprise the AOX1 or GAL1 promoter in yeast, and those for
expression in animal cells include the CMV, SV40, RVS-40 promoter and/or
CMV or SV40 enhancer. Further examples of suitable promoters are the
metallothionein I and polyhedrin promoters.
Suitable vectors are in particular T7-based expression vectors for
expression in bacteria (Rosenberg et al., Gene 56 (1987), 125) or pMSXND
for expression in mammalian cells (Lee and Nathans, J. Biol. Chem. 263
The DNA according to the invention can be inserted in a vector not only
for the purpose of recombinant production but also to inject using vectors
this DNA into patients where it codes for an antigen for therapeutic
purposes. In this connection, the DNA is attached in vivo by means of a
vector to antigen-presenting cells (APCs), e.g. dendritic cells, for HLA
presentation of CTAGE. Here, the vector containing the DNA according to
the invention can be injected in different ways: a) lipid-packed or
liposome-packed DNA or RNA, e.g. generally described by Nabel et al.,
Proc. Natl. Acad. Sci. U.S.A., Vol. 93, pages 15388-15393 (1996); b) by
means of a bacterium as a transport vehicle for the expression vector.
Suitable bacteria are e.g. (attenuated) listerias [e.g. Listeria
monocytogenes], salmonella strains [e.g. Salmonella spp.]. This method is
described generally by Medina et al., Eur. J. Immunol., 29, pages 693-699
(1999) and Guzman et al., Eur. J. Immunol. 28, pages 1807-1814 (199).
Reference is also made to WO 96/14087; Weiskirch et al., Immunological
Reviews, Vol. 158, pages 159-169 (1997) and U.S. Pat. No. 5,830,702; c) by
means of gene gun (Williams et al., Proc. Natl. Acad. Sci. U.S.A., Vol.
88, pages 2726-2730, 1991).
In a preferred embodiment, the vector containing the DNA molecules
according to the invention is a virus, e.g. an adenovirus, vaccinia virus
or an AAV virus, which is of use for a gene therapy. Retroviruses are
particularly preferred. Examples of suitable retroviruses are MoMuLV,
HaMuSV, MuMTV, RSV or GaLV. The above-mentioned viruses and the fowlpox
virus, canarypox virus, influenza virus or sindbis virus are also suited
as a basis for a vaccine. Such new vaccines, which after being
administered give the patient immunity against tumors, are described in N.
Restifo, Current Opinion in Immunology, 8, pages 658-663 1996), or Ying et
al., Nature Medicine, Vol. 5, No. 7, page 823 et seq., (1999), for
example. For the purpose of gene therapy the DNA molecules according to
the invention can also be transported to the target cells in the form of
colloidal dispersions. These comprise e.g. liposomes or lipoplexes (Mannino
et al., Biotechniques 6 (1988), 682).
General methods known in the art can be used to design vectors or plasmids
which contain the DNA molecules according to the invention and suitable
control sequences. These methods comprise e.g. in vitro recombination
techniques, synthetic methods and in vivo recombination methods, as
described in Sambrook et al., supra, for example.
The present invention also relates to host cells containing the above
described vectors. These host cells comprise bacteria, yeast, insect and
animal cells, preferably mammalian cells. The E. coli strains HB101, DH1,
x1776, JM101, JM109, BL21, XL1Blue and SG13009, the yeast strain
Saccharomyces cerevisiae and the animal cells L, 3T3, FM3A, CHO, COS,
Vero, HeLa, and the insect cells sf9 are preferred. Methods of
transforming these host cells, of phenotypically selecting transformants
and expressing the DNA molecules according to the invention using the
above described vectors are known in the art.
In order to produce immunity against tumors, it is also preferred to
transfect the DNA according to the invention into antigen-presenting cells
and give the patient these cells by way of injection. Here, a plasmid is
introduced in vitro into an antigen presenting cell (APCs), e.g. dendritic
cells, which then produce antigens and present individual peptides via HLA
molecules. In this connection, the plasmid DNA can be introduced into the
antigen-presenting cells in different ways: (a) as a naked DNA, e.g. by
means of gene gun or electroporation, (b) lipid-packed or liposome-packed
DNA or RNA (Nair et al., Nature Biotechnology, Vol. 16, page 364 et seq.
(1998)), (c) by means of a virus as a vector (Kim et al., J. of
Immunotherapy, 20(4), pages 276-286 (1997)), (d) by means of a bacterium
as a transport vehicle for the expression vector (Medina et al., Eur. J.
Immunol., 29, pages 693-699 (1999); Guzman et al., Eur. J. Immunol. 28,
pages 1807-1814 (1998)).
A clone which codes for a nucleic acid according to the invention
(CTAGE-1) was deposited with DSMZ, Deutsche Sammlung von Mikroorganismen
und Zellkulturen CmbH [German-type collection of microorganisms and cell
cultures], Mascheroder Weg 1b, 38124 Braunschweig, Germany, in accordance
with the Budapest Treaty under accession number DSM 13079 (=Escherichia
coli XL2-Blue pCTAGE-1) on Oct. 7, 1999.
The present invention also relates to a method of producing a protein
which is encoded by the above nucleic acids, comprising culturing the
above described host cells under conditions enabling the expression of the
protein (preferably stable expression) and obtaining the protein from the
culture. Suitable methods of recombinantly producing the protein are
generally known (see e.g. Holmgren, Annu. Rev. Biochem. 54 (1985), 237;
LaVallie et al., Bio/Technology 11 (1993), 187; Wong, Curr. Opin. Biotech.
6 (1995), 517; Romanos, Curr. Opin. Biotech. 6 (1995), 527; Williams et
al., Curr. Opin. Biotech. 6 (1995), 538; and Davies, Curr. Opin Biotech. 6
(1995), 543). Suitable purification methods (e.g. preparative
chromatography, affinity chromatography, e.g. immunoaffinity
chromatography, HPLC, etc.) are also generally known.
In another embodiment, the present invention relates to a protein encoded
by the DNA molecules according to the invention (CTAGE-1 or CTAGE-2) or
obtained according to the above method. The protein coding for CTAGE-2 is
shown in FIG. 3 (see Original
Patent). In this connection, it is pointed out that the protein according
to the invention can be modified according to common methods known in the
art. The modifications comprise substitutions, insertions or deletions of
amino acids, which modify the structure of the protein, its biological
activity being substantially maintained. The substitutions comprise
particularly "conservative" substitution of amino acid residues, i.e.
substitutions for biologically similar residues, e.g. the substitution of
a hydrophobic residue (isoleucine, valine, leucine, methionine, for
example) for another hydrophobic residue, or the substitution of a polar
residue for another polar residue (e.g. arginine for lysine, glutamic acid
for aspartic acid, etc.). Deletions may result in the production of
molecules markedly reduced in size, i.e. they lack amino acids at the
N-terminus or C-terminus, for example. In this connection, the variants
have a homology of at least 70%, preferably 80%, more preferably 90%, most
preferably 95, 96, 97, 98 or 99%, with the amino acid sequence derived
from the nucleotide sequence according to FIG. 1 or with the amino acid
sequence according to FIG. 3.
For the desired anti-tumor vaccination, it is also suited to give the
protein or one or more peptides derived therefrom by way of injection. For
this purpose, HLA-dependent peptide fragments are determined from the
sequence of the protein according to the invention by either corresponding
computer programs or experiments (e.g. phagocytotic uptake of the entire
protein, then analysis of the presenting peptides). They are produced
artificially by methods known to the person skilled in the art and then
given to the patient by way of injection (if necessary, with factors
stimulating the immune system, e.g. interferons, interleukins etc.). This
treatment shall effect that the APCs take up the peptides, present them
and thus stimulate in vivo the production of tumor-specific cytotoxic
T-cells. This principle is described generally by Melief et al., Current
Opinion in Immunology, 8, pages 651-657 (1996).
As described above, the protein according to the invention or fragments
thereof can be loaded in vitro on APCs in place of the vector. The loaded
cells are then injected into the patient's lymph nodes and provide
directly for the stimulation and replication of tumor-specific cytotoxic
T-cells (Nestle et al., Nature Medicine, Vol. 4, No. 3, page 328 et seq.
(1998); Schadendorf et al., in: Burg, Dummer, Strategies for
Immunointerventions in Dermatology, Springer Verlag, Berlin Heidelberg,
pages 399-409, 1997). For the purpose of vaccination it may be favorable
to modify individual amino acids, as described above, vis-a-vis the
wild-type antigen, since under certain circumstances it is in this way
possible to increase binding and improve effectiveness (Clay et al., The
Journal of Immunology 162: pages 1749-1755, 1999).
The present invention also relates to antibodies which recognize
specifically the above described protein CTAGE-1 or CTAGE-2. The
antibodies may be monoclonal, polyclonal or synthetic antibodies or
fragments thereof, e.g. Fab, Fv or scFv fragments. They are preferably
monoclonal antibodies. For the production it is favorable to immunize
animals, in particular rabbits or chickens for a polyclonal antibody and
mice for a monoclonal antibody, with an above (fusion) protein or with
fragments thereof. Further boosters of the animals can be made with the
same (fusion) protein or with fragments thereof. The polyclonal antibody
can then be obtained from the animal serum or egg yolk. The antibodies
according to the invention can be produced according to standard methods,
the protein encoded by the DNA molecules according to the invention or a
synthetic fragment thereof serving as an immunogen Monoclonal antibodies
can be prepared by the method described by Kohler and Milstein (Nature 256
(1975), 495) and Galfre (Meth. Enzymol. 73 (1981), 3), murine myeloma
cells being fused with spleen cells originating from immunized mammals.
These antibodies can be used e.g. for the immunoprecipitation of the above
discussed proteins or for isolating of related proteins from cDNA
expression libraries. The antibodies can be bound e.g. in immunoassays in
liquid phase or to a solid carrier. Here, the antibodies can be labeled in
different ways. Suitable markers and labeling methods are known in the
art. Examples of immunoassays are ELISA and RIA. The antibodies can also
be used therapeutically along with their diagnostic suitability. In this
connection, e.g. a protein of the CTAGE family, e.g. CTAGE-1 or CTAGE-2,
serves as a target for bispecific antibodies. Reference is made to
Kastenbauer et al. Laryngorhinootologie, 78(1), pages 31-35 (1999) and Cao
et al., Bioconj. Chem. 9(6), pages 635-644 (1998). As a result of antibody
administration, it is possible to counteract the effect of the CTAGE
proteins, which supports tumor growth and metastasis.
Furthermore, the use of CTAGE-1 or CTAGE-2 antisense DNA can serve for
inhibiting the translation of CTAGE-1 or CTAGE-2 and a therapeutic effect
can thus be exerted specifically to this gene. RNA/DNA hybrids form in the
corresponding tumor cells, preventing transcription in this way and
simultaneously degrading the hybrids (and thus the RNA) by RNaseH (Scanlon
et al., The Faseb Journal, Vol. 9, pages 1288-1296, 1995).
The present invention also relates to the use of the above described DNA
molecules, vectors, proteins and/or antibodies. They are used preferably
for producing a medicament for the diagnosis or treatment of tumoral
diseases in which CTAGE-1 or CTAGE-2 plays a role. The provision of a
vaccine which as described above is based on either the DNA or the
protein/peptide, is preferred.
These medicaments also contain, where appropriate, a pharmaceutically
compatible carrier. Suitable carriers and the formulation of such
medicaments are known to the person skilled in the art. Suitable carriers
comprise e.g. phosphate-buffered common salt solutions, water, emulsions,
e.g. oil/water emulsions, wetting agents, sterile solutions, etc. The
medicaments can be administered orally or parenterally. The methods of
parenteral administration comprise the topical, intra-arterial,
intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular,
intravenous, intraperitoneal or intranasal administration. The suitable
dosage is determined by the attending physician and depends on various
factors, e.g. the patient's age, sex and weight, the stage of the disease,
the kind of administration, etc.
The present invention also relates to a diagnostic composition which
contains the above-described DNA molecule or the antibody or to
combinations thereof with a suitable analytical agent, where appropriate.
The diagnostic composition is suited on the one hand to detect a tumoral
disease but also to carry out a follow-up.
The DNA molecule according to the invention, which is defined as outlined
above, can also be used as a probe to isolate DNA molecules which are
derived e.g. from another species or another organism and code for a
protein having an equal biological activity. For this purpose, the probe
has preferably a length of at least 10, more preferably at least 15 bases.
Suitable detection methods based on hybridization are known to the person
skilled in the art, e.g. Southern or Northern blot. Suitable labeling for
the probe is also known to the person skilled in the art and comprises
e.g. labeling with radioisotopes, bioluminescence, chemiluminescence,
fluorescent markers, metal chelates, enzymes, etc.
In addition, this can also be effected by PCR (Wiedemann et al., PCR
Methods Appl. 3, pages 551-564 (1994); Saiki et al., Nature 324, pages
163-166 (1986)) or "ligase chain reaction" (LCR) (Taylor et al., Curr.
Opin. Biotechnol. 6, pages 24-29 (1995); Rouwendal et al., Methods Mol.
Biol., pages 149-156 (1996)), the primers being derived from the sequence
in FIG. 1 or FIG. 2 and the person skilled in the art being able to design
suitable primers (as regards length, complementarity with respect to the
template, the area to be amplified, etc.) by common methods.
The present invention also relates to a method of diagnosing tumoral
diseases in vitro, comprising the steps of: isolating nucleic acid from
the patient, carrying out LCR or PCR with suitable primers or a
hybridization analysis with one or more suitable probes based on the
coding sequence of FIG. 1 or FIG. 2, detecting an amplified product or a
hybridization as a reference to the presence of a tumoral disease.
In connection with the above-mentioned method, it is possible to use
methods known to the person skilled in the art with respect to the
preparation of DNA or RNA from biological samples, the restriction
digestion of the DNA, the application of the restriction fragments onto
gels separating according to size, e.g. agarose gels, the production and
labeling of the probe and the detection of hybridization, e.g. via
"Southern blot" or in situ hybridization.
The above detection can also be carried out via PCR or LCR. Here, primers
are used, flanking the sequence according to the invention or suitable
partial regions. In this connection, amplification products of DNA from
the tissue in question, which differ from the amplification products of
DNA from healthy tissue as regards the occurrence of CTAGE-1 or
CTAGE-2-specific bands, are of diagnostic significance.
In an alternative embodiment, a method can be used which comprises the
steps of. isolating RNA from the patient, carrying out a Northern blot
analysis with one or more suitable probes, comparing the concentration
and/or length of CTAGE-1 or CTAGE-2 mRNA of the patient's sample with an
mRNA from a healthy person, the occurrence of CTAGE-1 or CTAGE-2 mRNA
referring to a tumoral disease as compared to control mRNA from normal
In connection with this method, it is possible to use procedures known to
the person skilled in the art with respect to the preparation of whole RNA
or poly(A)+RNA from biological samples, the application of RNAs onto gels
separating according to size, e.g. denaturing agarose gels, the production
and labeling of the probe and the detection via "Northern blot".
In another alternative embodiment, a possible disease can also be
diagnosed by a method comprising the steps of: obtaining a cell sample
from a patient, contacting the resulting cell sample with the above
described antibody according to the invention as a probe under conditions
enabling binding of the antibody, binding of the antibody referring to an
existing expression of CTAGE-1 or CTAGE-2, which is a reference to a
This detection can also be carried out using standard techniques known to
the person skilled in the art. He is also familiar with cell breaking-up
methods which enable the isolation of the protein such that it can be
contacted with the antibody. The bound antibody is detected preferably via
immunoassays, e.g. Western blot, ELISA, FACS or RIA or immunohistochemical
methods. The antibodies are also suited to catch CTAGE-1 or CTAGE-2
overexpressed in tumors so as to inhibit the growth of the tumor, since
there is reference to the fact that the occurrence of CTAGE-1 or CTAGE-2
does not only show the presence of tumors but also supports tumor growth
The present invention also relates to kits for carrying out the diagnostic
method according to the invention, which contain the antibody according to
the invention or a fragment thereof, a DNA molecule according to the
invention as a probe or a primer pair suitable for PCR or LCR and based on
the sequence of the DNA molecule according to the invention, optionally in
combination with a suitable detection means.
Depending on the design of the diagnostic method to be carried out with
the kit according to the invention, the DNA molecules, antibodies or
fragments thereof, which are contained in the kit, can be immobilized on a
Claim 1 of 8 Claims
1. An isolated nucleic acid
which codes for a protein of the CTAGE family and has expression in
malignant tumors and in ordinary testis tissue, wherein the nucleic acid
consists of the nucleic acid of SEQ ID NO: 1.
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