Compositions and methods for therapy and diagnosis of colon cancer
OwnerMadeleine Joy Meagher, Jiangchun Xu +1inventors
InventorsMadeleine Joy Meagher, Jiangchun Xu, Gordon E. King
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Abstract
Compositions and methods for the therapy and diagnosis of cancer, such as colon cancer, are disclosed. Compositions may comprise one or more colon tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a colon tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as colon cancer. Diagnostic methods based on detecting a colon tumor protein, or mRNA encoding such a protein, in a sample are also provided.
Claims59
An isolated polypeptide, comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (a) sequences recited in SEQ ID NOS:1-1556;
- (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions;
- and
- (c) complements of sequences of (a) or (b).
An isolated polynucleotide encoding at least 15 amino acid residues of a colon tumor protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigen-specific antisera is not substantially diminished, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence recited in any one of SEQ ID NOS:1-1556 or a complement of any of the foregoing sequences.
An isolated polynucleotide encoding a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence recited in any one of SEQ ID NOS:1-1556 or a complement of any of the foregoing sequences.
An isolated polynucleotide, comprising a sequence recited in any one of SEQ ID NOS:1-1556.
An isolated polynucleotide, comprising a sequence that hybridizes to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions.
An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a colon tumor protein that comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOS1-1556 or a complement of any of the foregoing polynucleotide sequences.
A vaccine comprising an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (a) sequences recited in SEQ ID NOS:1-1556;
- (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions;
- and
- (c) complements of sequences of (i) or (ii);
- in combination with an immunostimulant.
A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (a) sequences recited in SEQ ID NOS:1-1556;
- (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:
- 1-1556 under moderately stringent conditions;
- and
- (c) complements of sequences encoded by a polynucleotide recited in any one of SEQ ID NOS:1-1556;
- and thereby inhibiting the development of a cancer in the patient.
A method for removing tumor cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (i) polynucleotides recited in any one of SEQ ID NOS:1-1556;
- and
- (ii) complements of the foregoing polynucleotides;
- wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the antigen from the sample.
A method for stimulating and/or expanding T cells specific for a colon tumor protein, comprising contacting T cells with at least one component selected from the group consisting of:
- (a) polypeptides comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (i) sequences recited in SEQ ID NOS:1-1556;
- (ii) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions;
- and
- (iii) complements of sequences of (i) or (ii);
- (b) polynucleotides encoding a polypeptide of (a);
- and
- (c) antigen presenting cells that express a polypeptide of (a);
- under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.
A method for inhibiting the development of a cancer in a patient, comprising the steps of:
- (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:
- (i) polypeptides comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of
- (1) sequences recited in SEQ ID NOS:1-1556;
- (2) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions;
- and
- (3) complements of sequences of (1) or (2);
- (ii) polynucleotides encoding a polypeptide of (i);
- and
- (iii) antigen presenting cells that expresses a polypeptide of (i);
- such that T cells proliferate;
- and
- (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient.
A method for inhibiting the development of a cancer in a patient, comprising the steps of:
- (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:
- (i) polypeptides comprising at least an immunogenic portion of a colon tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
- (1) sequences recited in SEQ ID NOS:1-1556;
- (2) sequences that hybridize to a sequence recited in any one of SEQ ID NOS:1-1556 under moderately stringent conditions;
- and
- (3) complements of sequences of (1) or (2);
- (ii) polynucleotides encoding a polypeptide of (i);
- and
- (iii) antigen presenting cells that express a polypeptide of (i);
- such that T cells proliferate;
- (b) cloning at least one proliferated cell to provide cloned T cells;
- and
- (c) administering to the patient an effective amount of the cloned T cells, and thereby inhibiting the development of a cancer in the patient.
A method for determining the presence or absence of a cancer in a patient, comprising the steps of:
- (a) contacting a biological sample obtained from a patient with a binding agent that binds to a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOS:1-1556 or a complement of any of the foregoing polynucleotide sequences;
- (b) detecting in the sample an amount of polypeptide that binds to the binding agent;
- and
- (c) comparing the amount of polypeptide to a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient.
A method according to claim 42, wherein the antibody is a monoclonal antibody.
A method for monitoring the progression of a cancer in a patient, comprising the steps of:
- (a) contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOS:1-1556 or a complement of any of the foregoing polynucleotide sequences;
- (b) detecting in the sample an amount of polypeptide that binds to the binding agent;
- (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time;
- and
- (d) comparing the amount of polypeptide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
A method for determining the presence or absence of a cancer in a patient, comprising the steps of:
- (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NO:1-1556 or a complement of any of the foregoing polynucleotide sequences;
- (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide;
- and
- (c) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient.
A method for monitoring the progression of a cancer in a patient, comprising the steps of:
- (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NO:1-1556 or a complement of any of the foregoing polynucleotide sequences;
- (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide;
- (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time;
- and
- (d) comparing the amount of polynucleotide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
An oligonucleotide comprising 10 to 40 contiguous nucleotides that hybridize under moderately stringent conditions to a polynucleotide that encodes a colon tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOS:1-1556 or a complement of any of the foregoing polynucleotides.
Dependencies are inferred from the claim text.