Melanoma antigenic peptides

Details Melanoma antigenic peptides Melanoma antigenic peptides

1999-02-11

2001-10-23

Chan, Christina Y. (Department: 1644)

Chemistry: molecular biology and microbiology

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

Bacteria or actinomycetales; media therefor

C530S328000, C514S015800, C514S769000, C514S002600

Reexamination Certificate

active

06306640

ABSTRACT:

TECHNICAL FIELD
This invention relates to the field of human tumor vaccines and in particular, vaccine components useful against human melanoma.
BACKGROUND OF THE INVENTION
Tumor specific T cells, derived from cancer patients, will bind and lyse tumor cells. This specificity is based on their ability to recognize short amino acid sequences (epitopes) presented on the surface of the tumor cells by MHC class I and class II molecules. These epitopes are derived from the proteolytic degradation of intracellular proteins called tumor antigens encoded by genes that are either uniquely or aberrantly expressed in tumor or cancer cells.
The availability of specific anti-tumor T cells has enabled the identification of tumor antigens and subsequently the generation of cancer vaccines designed to provoke an anti-tumor immune response. Anti-tumor T cells are localized within cancer patients, including in the blood (where they can be found in the peripheral blood mononuclear cell fraction), in ascites fluid in ovarian cancer patients (tumor associated lymphocytes or TALs) or within the tumor itself (tumor infiltrating lymphocytes or TILs). Of these, TILs have been the most useful in the identification of tumor antigens and tumor antigen-derived peptides recognized by T cells.
Conventional methods to generate TILs involve mincing tumor biopsy tissue and culturing the cell suspension in vitro in the presence of the T cell growth factor interleukin-2 (IL-2). Over a period of several days, the combination of the tumor cells and IL-2 can stimulate the proliferation of tumor specific T cells at the expense of tumor cells. In this way, the T cell population is expanded. The T cells derived from the first expansion are subsequently mixed with irradiated tumor cells and cultured in vitro with IL2 to promote further proliferation and enrichment of tumor reactive T cells. After several rounds of in vitro expansion, a potent anti-tumor T cell population can be recovered and used to identify tumor antigens via conventional but tedious expression cloning methodology. Kawakani, Y. et al. (1994)
PNAS
91(9):3515-19.
This currently employed methodology used to generate tumor specific T cells in vitro is unreliable and the antigens identified by this method do not necessarily induce an anti-tumor immune response. Numerous experiments demonstrate that encounter of antigens by mature T cells often results in the induction of tolerance because of either ignorance, anergy or physical deletion. Pardoll (1998)
Nature Med
. 4(5):525-531.
Thus, a need exists to identify antigenic peptides that will induce an immune response for the generation of effective anti-cancer vaccines. This invention satisfies this need and provides related advantages as well.
DISCLOSURE OF THE INVENTION
Using a technique known as Solid-PHase Epitope REcovery (“SPHERE”) (described in WO 97/35035), synthetic gp 100 melanoma epitopes that are specifically recognized by tumor specific immune effector cells have been identified. Using SPHERE, a library of oligopeptides between 8 to 10 amino acids in length was made and screened for their specificity and ability to raise immune effector cells that specifically target and lyse melanoma cells.
Thus, this invention provides novel, synthetic polypeptide vaccines against human melanoma and methods for making these vaccines. Polynucleotides encoding these polypeptides are further provided herein.
This invention also provides antigen presenting cells (APC) that present the novel polypeptides on the cell surface and use of the APC in cancer therapy. Immune effector cells expanded in the presence of the APC are further provided herein. These compositions are useful as melanoma vaccines and in adoptive immunotherapy.
MODE(S) FOR CARRYING OUT THE INVENTION
Throughout this disclosure, various publications, patents and published patent specifications are referenced by an identifying citation. The disclosures of these publications, patents and published patent specifications are hereby incorporated by reference into the present disclosure to more fully describe the state of the art to which this invention pertains.
Definitions
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of immunology, molecular biology, microbiology, cell biology and recombinant DNA, which are within the skill of the art. See, e.g., Sambrook, et al.
MOLECULAR CLONING: A LABORATORY MANUAL
, 2
nd
edition (1989);
CURRENT PROTOCOLS IN MOLECULAR BIOLOGY
(F. M. Ausubel, et al. eds., (1987)); the series
METHODS IN ENZYMOLOGY
(Academic Press, Inc.):
PCR
2
: A PRACTICAL APPROACH
(M. J. MacPherson, B. D. Harnes and G. R. Taylor eds. (1995)), Harlow and Lane, eds. (1989)
ANTIBODIES, A LABORATORY MANUAL
, and
ANIMAL CELL CULTURE
(R. I. Freshney, ed. (1987)).
As used herein, certain terms may have the following defined meanings.
As used in the specification and claims, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a cell” includes a plurality of cells, including mixtures thereof.
The terms “polynucleotide” and “nucleic acid molecule” are used interchangeably to refer to polymeric forms of nucleotides of any length. The polynucleotides may contain deoxyribonucleotides, ribonucleotides, and/or their analogs. Nucleotides may have any three-dimensional structure, and may perform any function, known or unknown. The term “polynucleotide” includes, for example, single-, double-stranded and triple helical molecules, a gene or gene fragment, exons, introns, mRNA, tRNA, rRNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A nucleic acid molecule may also comprise modified nucleic acid molecules. “Oligonucleotide” refers to polynucleotides of between about 5 and about 100 nucleotides of single- or double-stranded DNA. Oligonucleotides are also known as oligomers or oligos and may be isolated from genes, or chemically synthesized by methods known in the art.
The term “genetically modified” means containing and/or expressing a foreign gene or nucleic acid sequence which in turn, modifies the genotype or phenotype of the cell or its progeny. In other words, it refers to any addition, deletion or disruption to a cell's endogenous nucleotides.
As used herein, “expression” refers to the process by which polynucleotides are transcribed into mRNA and translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA, if an appropriate eukaryotic host is selected. Regulatory elements required for expression include promoter sequences to bind RNA polymerase and transcription initiation sequences for ribosome binding. For example, a bacterial expression vector includes a promoter such as the lac promoter and for transcription initiation the Shine-Dalgarno sequence and the start codon AUG (Sambrook, et al. (1989) Supra ). Similarly, an eukaryotic expression vector includes a heterologous or homologous promoter for RNA polymerase II, a downstream polyadenylation signal., the start codon AUG, and a termination codon for detachment of the ribosome. Such vectors can be obtained commercially or assembled by the sequences described in methods well known in the art, for example, the methods described below for constructing vectors in general.
A “gene delivery vehicle” is defined as any molecule that can carry inserted polynucleotides into a host cell. Examples of gene delivery vehicles are liposomes, viruses, such as baculovirus, adenovirus and retrovirus, bacteriophage, cosmid, plasmid, fungal vectors and other recombination vehicles typically used in the art which have been described for expression in a variety of eukaryotic and prokaryotic hosts, and may be used for gene therapy as well as for simple protein expression.
A “viral vector” is defined as a recombinantly produced virus or viral particle that

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