Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Cancer cell or component thereof
Reexamination Certificate
1998-05-05
2003-03-25
Huff, Sheela (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Cancer cell or component thereof
C424S184100, C424S185100, 57, 57, 57, 57, 57, 57, 57
Reexamination Certificate
active
06537560
ABSTRACT:
FIELD OF THE INVENTION
This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.
BACKGROUND OF THE INVENTION
Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells (“Cellular and Molecular Immunology” (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S.; W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women (“Cellular and Molecular Immunology” (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S.; W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993)
Principles and Practice of Oncoloqy
7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993)
Principles and Practice of Oncology
7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma.
T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986)
Science
233:1318-1321). In addition, the secretion of IFN-&ggr; by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991)
J. Exp. Med.
173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988)
N Engl J Med
319:1676-1680; Rosenberg S. A. (1992)
J. Clin. Oncol.
10:180-199).
T cell receptors on CD8
+
T cells recognize a complex consisting of an antigenic peptide (9-10 amino acids for HLA-A2), &bgr;-2 microglobulin and class I major histocompatibility complex (MHC) heavy chain (HLA-A, B, C, in humans). Peptides generated by digestion of endogenously synthesized proteins are transported into the endoplastic reticulum, bound to class I MHC heavy chain and &bgr;2 microglobulin, and finally expressed in the cell surface in the groove of the class I MHC molecule. Therefore, T cells can detect molecules that originate from proteins inside cells, in contrast to antibodies that detect intact molecules expressed on the cell surface. Therefore, antigens recognized by T cells may be more useful than antigens recognized by antibodies.
Strong evidence that an immune response to cancer exists in humans provided by the existence of lymphocytes within melanoma deposits. These lymphocytes, when isolated, are capable of recognizing specific tumor antigens on autologous and allogeneic melanomas in an MHC restricted fashion. (Itoh, K. et al. (1986),
Cancer Res.
46: 3011-3017; Muul, L. M., et al. (1987),
J. Immunol.
138:989-995); Topalian, S. L., et al., (1989)
J. Immunol.
142: 3714-3725; Darrow, T. L., et al., (1989)
J. Immunol.
142: 3329-3335; Hom, S. S., et al., (1991)
J. Immunother.
10:153-164; Kawakami, Y., et al., (1992)
J. Immunol.
148: 638-643; Hom, S. S., et al., (1993)
J. Immunother.
13:18-30; O'Neil, B. H., et al., (1993)
J. Immunol.
151: 1410-1418). TIL from patients with metastatic melanoma recognize shared antigens including melanocyte-melanoma lineage specific tissue antigens in vitro (Kawakami, Y., et al., (1993)
J. Immunother.
14: 88-93; Anichini, A. et al., (1993) et al.,
J. Exp. Med.
177: 989-998). Anti-melanoma T cells appear to be enriched in TIL probably as a consequence of clonal expansion and accumulation at the tumor site in vivo (Sensi, M., et al., (1993)
J. Exp. Med.
178:1231-1246). The fact that many melanoma patients mount cellular and humoral responses against these tumors and that melanomas express both MHC antigens and tumor associated antigens (TAA) suggests that identification and characterization of additional melanoma antigens will be important for immunotherapy of patients with melanoma.
Peripheral blood lymphocytes have been used to identify potential melanoma tumor antigens. Van Der Bruggen et al. (1991)
Science
254: 1643-1647 has characterized a gene coding for a melanoma antigen, designated MAGE-1, using T cell clones established from the peripheral blood of patients who were repetitively immunized in vivo with mutagenized tumor cells. Cytotoxic T-cells derived from the peripheral blood lymphocytes of patients with melanoma were used to identify a potential antigenic peptide encoding MAGE-1 (Traversari, C., et al. (1992)
J. Exp. Med.
176:1453-1457). Brichard et al. (1993)
J. Exp. Med.
178:489-495 has also characterized a gene encoding a melanoma antigen designated tyrosinase using peripheral blood lymphocytes from patients who were sensitized by repetitive in vitro stimulation with tumor. Further support for the therapeutic potential of melanoma antigens is provided by Brown et al. (U.S. Pat. No. 5,262,177). Brown et al. (U.S. Pat. No. 5,262,177) relates to a recombinant vaccinia virus-based melanoma vaccine where the melanoma antigen p97 is reported to show a protective effect from tumor cell challenge in a murine model. Characterization of additional melanoma antigens is important for the development of new strategies for cancer immunotherapy, in particular for melanoma.
SUMMARY OF THE INVENTION
This invention relates, in general, to nucleic acid sequences encoding melanoma antigens recognized by T-lymphocytes (MART-1) and protein and peptides encoded by these sequences. This invention further provides bioassays for these nucleic acid sequences, proteins and peptides. This invention also provides peptides which have been derived from the MART-1 amino acid sequence and modified to enhance their immunogenocity. This invention also provides therapeutic uses for the nucleic acid sequences, proteins, peptides or modified peptides described herein.
It is a general object of the present invention to provide a substantially purified and isolated nucleic acid sequence which encodes for the MART-1 melanoma antigen.
It is another object of this invention to provide a recombinant molecule comprising a vector and all or part of the nucleic acid sequence encoding MART-1.
It is another object of this invention to produce recombinant proteins encoded by all or part of the nucleic acid sequence encoding MART-1.
It is a further object of this invention to provide monoclonal or polyclonal antibodies reactive with the MART-1 protein, peptides or portions thereof.
It is an object of this invention to provide methods of detecting the MART-1 gene or MART-1 mRNA in a biological sample.
It is another object of this invention to provide methods of detecting the MART-1 protein or peptides in a biological sample.
It is an object of this invention to provide diagnostic methods for human disease, in particular for melanomas and metastatic melanomas.
It is a further object of this invention to provide methods for prophylactic or therapeutic uses involving all or part of the nucleic acid sequence encoding MART-1 and its corresponding protein or peptides derived from the MART-1 amino acid sequence.
It is also an object of this invention to provide melanoma vaccines comprising all or part of the nucleic acid sequence encoding MART-1 or its corresponding protein for preventing or treating melanoma.
It is a further object of this invention
Kawakami Yutaka
Rosenberg Steven A.
Huff Sheela
Leydig , Voit & Mayer, Ltd.
The United States of America as represented by the Department of
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