gp75 as a tumor vaccine for melanoma

Details gp75 as a tumor vaccine for melanoma gp75 as a tumor vaccine for melanoma

1995-03-24

2001-01-02

Allen, Marianne P. (Department: 1631)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C435S320100, C435S325000, C536S023500

Utility Patent

active

06168946

ABSTRACT:

Throughout this application various publications are referenced. The disclosure of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully described the state of the art to which this invention pertains.
BACKGROUND OF THE INVENTION
The molecular identification of immunogenic determinants on human cancer cells provides a basis for understanding the immune response to cancer. On human melanoma cells, two classes of antigens have received particular attention as targets for immune recognition: 1) unique antigens expressed only by autologous melanoma cells (Old, L. J. (1981), Cancer immunology: The search for specificity. G. H. A. Clowes Memorial Lecture,
Cancer Res.
41:361; Carey, T. E., T. Takahashi, L. A. Resnick, H. F. Oettgen, and L. J. Old. (1976), Cell surface antigens of human malignant melanoma. I. Mixed hemadsorption assay for humoral immunity to cultured autologous melanoma cells,
Proc. Natl. Acad. Sci. USA.
73:3278; Real, F. X., M. J. Mattes, A. N. Houghton, H. F. Oettgen, K. O. Lloyd, and L. J. Old. (1984), Class 1 (unique) antigens of human melanoma: Identification of a 90,000 dalton cell surface glycoprotein by autologous antibody,
J. Exp. Med
160:1219) and 2) differentiation antigens normally expressed by cells of the melanocytic lineage (Houghton, A. N., M. C. Taormina, H. Ikeda, T. Watanabe, H. F. Oettgen, and L. J. Old. (1980), Serological survey of normal humans for natural antibody to cell surface antigens of melanoma,
Proc. Natl. Acad. Sci. USA.
77:4260; Houghton, A. N., M. Eisinger, A. P. Albino, J. G. Cairncross, and L. J. Old. (1982), Surface antigens of melanocytes and melanoma: Markers of melanocyte differentiation and melanoma subsets,
J. Exp. Med.
156:1755; Houghton, A. N., F. X. Real, L. J. Davis, C. Cardon-Cardo, and L. J. Old. (1987), Phenotypic heterogeneity of melanoma: Relation to the differentiation program of melanoma cells,
J. Exp. Med.
164:812). Differentiation antigens of melanocytes have been defined by their relationship to other well-defined phenotypic traits expressed during melanocyte differentiation (Houghton, A. N., M. Eisinger, A. P. Albino, J. G. Cairncross, and L. J. Old. (1982), Surface antigens of melanocytes and melanomas: Markers of melanocyte differentiation and melanomas subsets,
J. Exp. Med.
156:1755; Houghton, A. N., F. X. Real, L. J. Davis, C. Cardon-Cardo, and L. J. Old. (1987) Phenotypic heterogeneity of melanoma: Relation to the differentiation program of melanoma cells,
J. Exp. Med.
164:812), the most distinctive being the synthesis of the pigment melanin within melanosomes.
Clinical observations have suggested that an immune response directed against antigens expressed by normal pigment cells might influence the course of metastatic melanoma. Specifically, Vitiligo and hypopigmentation in patients with melanoma have been associated with a good prognosis (Nordlund, J. J., J. M. Kirkwood, B. M. Forget, G. Milton, D. M. Albert, and A. B. Lerner. (1983) Vitiligo in patients with metastatic melanoma: a good prognosis sign,
J. Am. Acad. Dermatol.
9:689; Bystryn, J. C., D. Rigel, R. J. Friedman, and A. Kopf. (1987) Prognostic significance of hypopigmentation in malignant melanoma,
Arch. Dermatol.
123:1053.) In this regard, melanosomal antigens can be recognized by the immune system. This has been demonstrated by immunoprecipitation of a gp75 antigen from autologous melanoma cells by serum IgG antibodies of a patient with metastatic melanoma (Mattes, J. M., T. M. Thomson, L. J. Old, and K. O. Lloyd. (1983) A pigmentation-associated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum,
Int. J. Cancer.
32:717). The gp75 antigen is a melanosomal polypeptide that is the most abundant glycoprotein synthesized by pigmented melanocytes and melanomas. (Tai, T., M. Eisinger, S. Ogata, and K. O. Lloyd. (1983) Glycoproteins as differentiation markers in human malignant melanoma and melanocytes,
Cancer Res.
43:2773). Epidermal melanocytes, benign pigmented lesions, and primary and metastatic melanomas express gp75, but other cell types do not (Thomson, T. M., F. X. Real, S. Murakami, C. Cardon-Cardo, L. J. Old, and A. N. Houghton. (1988) Differentiation antigens of melanocytes and melanoma: Analysis of melanosome and cell surface markers of human pigmented cells with monoclonal antibodies,
J. Invest. Dermatol.
90:459). In the present invention, it is demonstrated that gp75 cDNA had approximately 90% identity with the derived amino acid and nucleotide sequences of a mouse gene that maps to the
b
(brown) locus. The brown locus is a site that determines coat color and influences the type of melanin synthesized, suggesting that gp75 may regulate or influence the type of melanin synthesized.
The fact that IgG antibodies in sera of a patient with metastatic melanoma have been shown to immunoprecipitate gp75 demonstrates that immunological tolerance against gp75 can be broken. This invention therefore provides expression vectors comprising gp75 cDNA for use as a vaccine against melanoma, whereby the amino acid sequences of peptides were determined from gp75 polypeptide, which was isolated and purified by the mouse monoclonal antibody TA99,and whereby cDNA clones were isolated by screening with oligonucleotides based on the peptide sequences.
SUMMARY OF THE INVENTION
The present invention provides an isolated nucleic acid molecule whose sequence encodes the amino acid sequence for gp75 or a fragment thereof.
The present invention further provides an isolated cDNA molecule of the gp75 nucleic acid molecule as well as an isolated cDNA molecule of a fragment of the gp75 nucleic acid molecule having the nucleotide sequence shown in FIG.
3
and the amino acid sequence derived therefrom.
This invention also provides vaccines for stimulating or enhancing in a subject to whom the vaccine is administered production of antibodies directed against gp75.
This invention further provides a method for stimulating or enhancing in a subject production of antibodies directed against gp75. The method comprises administering to the subject a vaccine of this invention in a dose effective for stimulating or enhancing production of the antibodies.
This invention further provides methods for treating, preventing or delaying recurrence of cancer. The methods comprise administering to the subject a vaccine of this invention in a dose effective for treating, preventing or delaying recurrence of cancer.


REFERENCES:
patent: H819 (1990-09-01), Srivastava et al.
patent: 4414148 (1983-11-01), Jansen et al.
patent: 4591572 (1986-05-01), Matteo et al.
patent: 4798790 (1989-01-01), Thomson et al.
patent: 4806628 (1989-02-01), Albino et al.
patent: 4808704 (1989-02-01), Old et al.
patent: 4851510 (1989-07-01), Khan
patent: 5009995 (1991-04-01), Albino et al.
patent: 5059523 (1991-10-01), Rettig et al.
patent: 5141742 (1992-08-01), Brown et al.
patent: 5262117 (1993-11-01), Brown et al.
patent: 0208902 (1987-11-01), None
patent: 178931 (1987-01-01), None
patent: WO9102062 (1993-02-01), None
Tai, T. et al., (1983) Glycoproteins as Differentiation Markers in Human Malignant Melanoma and Melanocytes,Cancer Research, 43:2773-2779; (Exhibit C).
Vijayasaradhi, S. and Houghton, A., (1991) Purification of an Autoantigenic 75-kDa Human Melanosomal Glycoprotein,Int. J. Cancer, 47:298-303. (Exhibit D).
Broome, S., and Gilbert, W., (1978) “Immunological Screening Method to Detect Specific Translation Products”,Proc. Natl. Acad. Sci., 75:2746-49 (Exhibit D).
Kwon et al., (1991) “A Melanocyte-Specific Gene, Pmel 17, Maps Near the Silver Coat Color on Mouse Chromosome 10 and is in a Syntenic Region on Human Chromosome 12”,Proc. Natl. Acad. Sci. USA, 88:9228-32 (Exhibit E).
Vijayasaradhi, S. et al., (1991) “Biosynthesis and Intracellular Movement of the Melanosomal Membrane Glycoprotein GP75, the Human b (Brown) Locus Product”,Experimental Cell Research, 196:233-40 (Exhibit F).
Jackson, Ian J., (1988) “A cDNA encoding Tyrosinase-related Protein Maps to the Bro

Affiliated with

Also associated with

Rating

gp75 as a tumor vaccine for melanoma does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with gp75 as a tumor vaccine for melanoma, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and gp75 as a tumor vaccine for melanoma will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2507259