Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-09-09
2004-02-03
Ungar, Susan (Department: 1642)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091100, C435S091200, C435S094000, C536S023500, C536S024300, C536S024310
Reexamination Certificate
active
06686147
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to nucleic acids and encoded polypeptides which are cancer associated antigens. The invention also relates to agents which bind the nucleic acids or polypeptides. The nucleic acid molecules, polypeptides coded for by such molecules and peptides derived therefrom, as well as related antibodies and cytolytic T lymphocytes, are useful, inter alia, in diagnostic and therapeutic contexts.
BACKGROUND OF THE INVENTION
The mechanism by which T cells recognize foreign materials has been implicated in cancer. A number of cytolytic T lymphocyte (CTL) clones directed against autologous melanoma antigens, testicular antigens, and melanocyte differentiation antigens have been described. In many instances, the antigens recognized by these clones have been characterized.
The use of autologous CTLs for identifying tumor antigens requires that the target cells which express the antigens can be cultured in vitro and that stable lines of autologous CTL clones which recognize the antigen-expressing cells can be isolated and propagated. While this approach has worked well for melanoma antigens, other tumor types, such as epithelial cancers including breast and colon cancer, have proved refractory to the approach.
Recent progress in the identification of human tumor antigens has generated a repertoire of target molecules for use in antigen-specific tumor vaccines. The continued expansion of this repertoire allows for the potential development of polyvalent cancer vaccines that can be applied to several tumor types and may help circumvent some of the difficulties associated with active immunotherapy, such as tumor heterogeneity and antigen loss. Human tumor antigens fall into several categories, including autoimmunogenic differentiation antigens (e.g., tyrosinase), mutated gene products (e.g., beta catenin), oncogenes (e.g., Her2
eu), and a collection of immunogenic proteins that have an expression pattern restricted to testis, as well as a proportion of various cancers. These proteins, referred to as cancer-testis antigens (CT antigens, CTAs), were initially identified in cancer patients by expression cloning using either the autologous cellular or humoral immune response as the election criteria. The first members of this group were those molecules defined by cytotoxic T-lymphocyte (CTL) recognition such as the MAGE, BAGE, and GAGE antigens. Subsequently, by employing autologous antibody recognition, the SEREX (serological analysis of recombinant cDNA expression libraries) method uncovered other members of this group including the HOM-MEL-40/SSX2, NY-ESO-1, SCP1 and CT7 antigens.
The SEREX procedure was described by Sahin et al. (
Proc. Natl. Acad. Sci. USA
92:11810-11813, 1995). Also, see U.S. Pat. No. 5,698,396, incorporated herein by reference. According to this approach, autologous antisera are used to identify immunogenic protein antigens expressed in cancer cells by screening expression libraries constructed from tumor cell cDNA. Antigen-encoding clones so identified have been found to have elicited an high-titer humoral immune response in the patients from which the antisera were obtained. Such a high-titer IgG response implies helper T cell recognition of the detected antigen. These tumor antigens can then be screened for the presence of MHC/HLA class I and class II motifs and reactivity with CTLs.
More recently, non-immunological techniques such as representational difference analysis (RDA) have led to the identification of molecules such as MAGE-C1 that has an expression profile similar to CT antigens. A standardized nomenclature has been proposed for organizing the CT antigens into families. Due to a general lack of functional information, it is based on their order of discovery, i.e., sequentially, MAGE, BAGE, GAGE, HOM-MEL-40/SSX2, NY-ESO-1, SCP-1, CT7 and CT8.
Since individual CTAs are expressed only in a variable proportion of tumors of a given entity, the availability of additional CTAs would significantly enlarge the proportion of patients who are potentially eligible for therapeutic interventions. Despite the fact that the pool of available tumor antigens has grown since the introduction of SEREX, the proportion of antigen-negative tumors is still high. Thus there presently is a need for additional cancer antigens for development of therapeutics and diagnostics applicable to a greater number of cancer patients having various cancers.
SUMMARY OF THE INVENTION
The invention provides, inter alia, isolated nucleic acid molecules, expression vectors containing those molecules and host cells transfected with those molecules. The invention also provides isolated proteins and peptides, antibodies to those proteins and peptides and CTLs which recognize the proteins and peptides. Fragments including functional fragments and variants of the foregoing also are provided. Kits containing the foregoing molecules additionally are provided. The foregoing can be used in the diagnosis, monitoring, research, or treatment of conditions characterized by the expression of BRDT/CT9 and optionally one or more additional cancer associated antigens.
The invention involves the surprising discovery that a previously known gene, BRDT, is expressed in individuals who have cancer. In addition, the invention also includes the characterization of expression of CT antigens in individuals with lung cancer. These individuals have serum antibodies against the proteins (or fragments thereof) encoded by these genes. Thus, abnormally expressed genes are recognized by the host's immune system and therefore can form a basis for diagnosis, monitoring and therapy.
The invention involves the use of a single material, a plurality of different materials and even large panels and combinations of materials. For example, a single gene, a single protein encoded by a gene, a single functional fragment thereof, a single antibody thereto, etc. can be used in methods and products of the invention. Likewise, pairs, groups and even panels of these materials and optionally other cancer associated antigen genes and/or gene products can be used for diagnosis, monitoring and therapy. The pairs, groups or panels can involve 2, 3, 4, 5 or more genes, gene products, fragments thereof or agents that recognize such materials. A plurality of such materials are not only useful in monitoring, typing, characterizing and diagnosing cells abnormally expressing such genes, but a plurality of such materials can be used therapeutically. An example of this is the use of a plurality of such materials prophylactically or acutely for the prevention, delay of onset, amelioration, etc. of cancer in cells which express or will express such genes. Any and all combinations of the genes, gene products, and materials which recognize the genes and gene products can be tested and identified for use according to the invention. It would be far too lengthy to recite all such combinations; those skilled in the art, particularly in view of the teaching contained herein, will readily be able to determine which combinations are most appropriate for which circumstances.
As will be clear from the following discussion, the invention has in vivo and in vitro uses, including for therapeutic, diagnostic, monitoring and research purposes. One aspect of the invention is the ability to fingerprint a cell expressing a number of the genes identified according to the invention by, for example, quantifying the expression of such gene products. Such fingerprints will be characteristic, for example, of the stage of the cancer, the type of the cancer, or even the effect in animal models of a therapy on a cancer. Cells also can be screened to determine whether such cells abnormally express the genes identified according to the invention.
The invention, in part, relates to compositions and methods of use thereof of nucleic acid molecules and polypeptides. For simplicity, these nucleic acid molecules and polypeptides have been classified into different groups. NA Group 1 molecules represent (a) nucleic acid molecules coding for a cancer asso
Chen Yao-Tseng
Gure Ali
Old Lloyd J.
Scanlan Matthew J.
Williamson Barbara
Davis Minh Tam
Ludwig Institute for Cancer Research
Ungar Susan
Wolf Greenfield & Sacks P.C.
LandOfFree
Cancer associated antigens and uses therefor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cancer associated antigens and uses therefor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cancer associated antigens and uses therefor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3304932