Medical College of Georgia Research Institute, Inc.

Other

Jeffrey Roberts Lee

James R Goldenring

P Henry Schmidt

Andrew L Mellor

David Munn

Gregory S Ray

The present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. Also disclosed are kits for assessing the relative risk of tumor progression in a subject. For example, disclosed are kits for assessing the relative risk of tumor progression in a subject and having reagents for detection of the enzyme indoleamine 2,3-dioxygenase (IDO) in a sample of tissue from a tumor or tumor draining lymph node from a subject, wherein the reagents are packaged in at least one individual container. The kits may include reagents for detection of cell surface or immunohistochemical markers associated with high IDO expression by APCs such as DO, CD123, CD11c or CCR6.

Kits to assess the risk of tumor progression

It has been determined that a specific metaplastic lineage that contains immunoreactivity for a trefoil polypeptide, spasmolytic peptide, is associated with and gives rise to the vast majority of human adenocarcinomas. The identification of this Spasmolytic Polypeptide Expressing Metaplasia (SPEM) is a major factor for grading of biopsies of the stomach to assess risk for gastric cancer. It also forms the basis of a method for serological screening for those at risk for gastric cancer. In a preferred embodiment, antibodies to spasmolytic peptide (hSP) are used in immunostaining of biopsies of gastric tissue obtained by endoscopy for grading biopsies. Those patients having these cells, characterized by a morphology more typical of a type of cell present normally in the intestine and not stomach, Brunner's gland cells, are at risk of developing adenocarcinoma. Since these cells express hSP, antibodies or nucleic acid probes hybridizing to mRNA encoding hSP, can be used for rapid detection of the cells in tissue biopsies. The antibodies can also be used in serological tests for screening and following patients at risk for gastric cancer. In combination with evidence of previous or present invention with , the tests are predictive of the likelihood of developing adenocarcinoma.

Screen for risk for gastric adenocarcinoma

It has been determined that a specific metaplastie lineage that contains immunoreactivity for a trefoil polypeptide, spasmolytic peptide, is associated with and gives rise to the vast majority of human adenocarcinomas. The identification of this Spasmolytic Polypeptide Expressing Metaplasia (SPEM) is a major factor for grading of biopsies of the stomach to assess risk for gastric cancer. It also forms the basis of a method for serological screening for those at risk for gastric cancer. In a preferred embodiment, antibodies to spasmolytic peptide (hSP) are used in immunostaining of biopsies of gastric tissue obtained by endoscopy for grading biopsies Those patients having these cells, characterized by a morphology more typical of a type of cell present normally in the intestine and not stomach, Brunner's gland cells, are at risk of developing adenocarinoma. Since these cells express hSP, antibodies or nucleic acid probes hybridizing to mRNA encoding hSP, can be used for rapid detection of the cells in tissue biopsies. The antibodies can also be used in serological tests for screening and following patients at risk for gastric cancer. In combination with evidence of previous or present infection with , the tests are predictive of the likelihood of developing adenocarcinoma.

Screen for gastric adenocarcinoma

A method of detecting dysplastic regions within epithelial tissue samples is sensitive enough to detect and distinguish between low grade and high grade dysplastic regions. The method uses probes specific for expression and accumulation of substances within a particular intracellular region from a defect in apical membrane trafficking (trafficking markers) and in the preferred embodiment correlates the trafficking marker levels with the presence of an oncogene such as p53. If low grade dysplasia is present, trafficking markers are detected in a distinctive perinuclear pattern. Previous studies have demonstrated a high correlation of p53 over-expression with high grade dysplasia and adenocarcinoma. Detection of p53 is shown to be mutually exclusive of detection of trafficking markers. Therefore, dual detection for both the trafficking markers and p53 provides an accurate method for more precise grading of biopsies. This definitive assay and grading assists in identifying populations at risk for progression to adenocarcinoma. Preferred trafficking markers include Rab11, Rab25, g-adaptin and mannose-6-phosphate receptor.

Growing community of inventors

Martinez, GA, United States of America

Jeffrey Roberts Lee