An analysis of immunohistochemical detection of her2neu protein p185her2 in feline mammary carcinoma

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An analysis of immunohistochemical detection of her2neu protein p185her2 in feline mammary carcinoma

What is claimed is: Antigenic polypeptides of HER2, for breaking tolerance to the self HER2 of an animal subject, said antigenic polypeptides including at least one point mutation in the extracellular domain of HER2. Isolated antigenic polypeptides for inducing immune response against HER2 in a subject of a mammalian species, said polypeptides comprising at least the extracellular domain of the HER2 of an animal species, said extracellular domain including an amino acid substitution of glutamine with lysine Q-Kor with a conservative amino acid of lysine, said substitution being at position of mature feline HER2, or at a homologous position of the mature HER2 of another animal species.

The antigenic polypeptides according to claim 3 wherein said antigenic polypeptides comprise the signal peptide and extracellular and transmembrane domains of HER2 precursor HER2 and said amino acid substitution of glutamine with lysine Q-K or a conservative amino acid of lysine, is at position of precursor feline HER2, or at a homologous position of the precursor HER2 of another animal species.

A gene expression construct comprising a nucleic acid sequence encoding an antigenic polypeptide of the HER2 of an animal species, said antigenic polypeptide comprising at least the extracellular domain of HER2, including an amino acid substitution of glutamine for lysine Q-K or for a conservative amino acid of K, said substitution being encoded at amino acid of mature feline HER2, or at an analogous amino acid of the mature HER2 of another animal species, said gene construct additionally including at least one promoter operatively linked to said nucleic acid sequence encoding a HER2 polypeptide, for expression of said antigenic peptide in a living cell.

The gene expression construct according to claim 9, wherein said nucleic acid sequence additionally encodes the signal peptide of HER2 precursor HER2and said amino acid substitution of glutamine for lysine Q-K or for a conservative amino acid of K, is encoded at amino acid of precursor feline HER2, or at the homologous amino acid of the precursor HER2 of another animal species, The gene construct according to claim 9, wherein said promoter is the cytomegalovirus CMV promoter.

An analysis of immunohistochemical detection of her2neu protein p185her2 in feline mammary carcinoma

A vaccine composition for inducing immunity to HER2 in a mammalian subject, comprising an effective amount of a gene expression construct according to claim 9, and an effective amount of an adjuvant. The vaccine composition according to claim 16, wherein said adjuvant is granulocyte macrophage colony stimulating factor GM-CSF.

The vaccine composition according to claim 17, wherein said GM-CSF is delivered to the mammalian subject as an expression vector comprising a polynucleotide encoding GM-CSF, for expression of said polynucleotide in the mammalian subject.

A method for inducing immune response to HER2 in a mammalian subject, comprising the steps of administering an effective amount of the vaccine composition according to claim 16, and inducing an immune response to HER2. A method for inducing immune response to HER2 in a mammalian subject, including the steps of: The method according to claim 21, wherein the step of administering an effective amount of an immunological adjuvant is further defined as administering an effective amount of GM-CSF.

The method according to claim 21, wherein the mammalian subject is further defined as a subject hosting a population of HER2-expressing pathological cells, additionally including the step of eliminating or reducing the population of HER2-expressing pathological cells.

The method according to claim 25, wherein the HER2 expressing pathological cells are further defined as mammary carcinoma cells. A method for inducing immune response to HER2 in a cat, including the steps of: The method according to claim 27, wherein the cat is further defined as a cat hosting a population of HER2-expressing pathological cells, additionally including the step of eliminating or reducing the population of HER2-expressing pathological cells.

The method according to claim 30, wherein the HER2 expressing pathological cells are further defined as mammary carcinoma cells.

Species Glossary

Antigenic polypeptides for inducing immune response against HER2 in a mammalian subject, said polypeptides comprising at least the extracellular and transmembrane domains of human HER2, said extracellular domain including an amino acid substitution selected from the following amino acid substitutions: A gene expression construct comprising a nucleic acid sequence encoding an antigenic polypeptide of HER2, said nucleic acid sequence encoding a substituted HER2 polypeptide selected from the group including: The gene expression construct according to claim 34, wherein said nucleic acid sequence is selected from the group consisting of: A vaccine composition for inducing immunity to HER2 in a mammalian subject, comprising an effective amount of the gene expression construct according to claim 35, and an effective amount of an adjuvant.

The vaccine composition according to claim 36, wherein said adjuvant is granulocyte macrophage colony stimulating factor GM-CSF The vaccine composition according to claim 37 wherein said GM-CSF is delivered to the mammalian subject as an expression vector comprising a polynucleotide encoding GM-CSF, for expression of said polynucleotide in the mammalian subject.

Monoclonal antibodies selective for substituted HER2 polypeptides, the substituted HER2 polypeptides being selected from the group consisting of: A diagnostic method of determining whether a mammalian subject is sufficiently immunocompetent to respond to immunotherapy directed at self HER2, including the steps of: The diagnostic method of claim 41, wherein the vaccine is selected from the group consisting of the vaccine according to claim 14 and the vaccine according to claim The diagnostic method according to claim 41, wherein the step of determining that an immune response is induced is further defined as the step of determining whether there a T cell response has been induced, a B cell response has been induced, or a mixed T and B cell response has been induced.

The invention is related to a modification of the Herceptin antibody, so as to maintain the antibody properties, while making the antibody directly recognizable in immunohistochemistry. Description The present invention concerns the in vitro localization of HER2 receptor in breast cancer cells.
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The Government has certain rights in the invention. The invention related particularly to the induction of anti-HER2 immunity for the treatment and prevention of mammary carcinomas and other HER2 expressing tumors in humans and other mammalian species.

Most tumor antigens are self antigens showing little or no difference from their normal counterparts in amino acid sequence and three dimensional structure. The immune system generally becomes tolerant to self antigens early in life. T lymphocyte clones specifically reactive to self antigens are either deleted or anergized during thymic development, or are kept in check at the periphery, mainly by diverse populations of regulatory T cells Treg.

Especially important are natural Treg which develop in the thymus upon high affinity recognition of antigens in the thymic stroma Colombo and Piconese, It is often impossible to predict an antigen and immunization protocol that will break tolerance to a self antigen to achieve effective vaccination.

This problem has defeated the development of many vaccines intended to induce immune response against tumor antigens Wei et al, HER2 receptors include an extracellular domain ECD of about amino acids, a single membrane-spanning transmembrane region TMand an intracellular domain ICD including a cytoplasmic tyrosine kinase.

Instead, it acts as a co-receptor, the preferred binding partner of the other HER family receptors. Ligand binding brings about heterodimerization of HER family receptors with HER2, leading to tyrosine kinase activation, and the activation of downstream signaling pathways.Dec 13,  · The invention provides a method for more effective treatment of patients susceptible to or diagnosed with tumors overexpressing HER2, as determined by a .

HER2 gene is amplified in a subset of feline mammary carcinomas despite the HER2 positive or equivocal protein expression, but it remains to be determined if the HER2 amplification is a gene.

Photomicrograph of a breast carcinoma displaying HER-2/neu gene amplification by FISH, mRNA enhanced expression, and overexpression of the oncoprotein by immunohistochemistry. Most of the nuclear area of the tumor cells contains large confluent black metallic gold signal generated through autometallography.

Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER-2/neu protooncogene encodes a kDa transmembrane tyrosine. Approximately 25–30% of human MGT demonstrate HER-2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis.

No reports have been published, to date, investigating the expression of Her-2/neu in cats or cats with spontaneous mammary tumours.

Breast cancer and Her2 gene. Salvar. Her2 Gene and Breast Cancer.

Her2 Gene and Breast Cancer - [PDF Document]