Claudins as Markers for Early Detection, Diagnosis, Prognosis and as Targets of Therapy for Breast and Metastatic Brain or Bone Cancer
AssigneeThe Johns Hopkins University
InventorsSaraswati V. Sukumar, Scott L. Kominsky
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Abstract
Methods of diagnosis, prognosis, and treatment of breast cancer, and of metastatic brain cancer, are provided The diagnostic and prognostic methods involve the immunohistochemical detection of the level of expression of the proteins claudin 1, 3, 4, and 7 in tissue or cell samples. Claudins 1 and 7 are underexpressed in the majority of breast cancers, and claudins 3 and 4 are overexpressed. The methods of treatment involve the use of Clostridium perfringens enterotoxin (or a variant thereof) to lyse metastatic cancer cells in the brain and bone that overexpress claudins 3 and 4.
Claims23
1-23. (canceled)
A method of killing cancer cells that express claudin-3 or claudin-4 or both claudin-3 and claudin-4, comprising the step of
- exposing said cancer cells to Clostridium perfringens enterotoxin or a fragment of Clostridium perfringens enterotoxin,
- wherein said step of exposing kills said cancer cells.
A method of killing cancer cells that express claudin-3 or claudin-4 or both claudin-3 and claudin-4, comprising the step of
- exposing said cancer cells to antibodies recognizing claudin-3 or claudin-4, or both, and which are associated with cytotoxic agents,
- wherein said step of exposing kills said cancer cells.
A method for diagnosing metastatic breast, colon or lung cancer in a patient in need thereof, comprising the steps of
- determining a level of expression of claudin 3 or claudin 4 or both claudins 3 and 4 in cells obtained from brain or bone tissue from said patient, and
- assessing whether claudin 3 or claudin 4 or both claudins 3 and 4 are expressed in said cells at a level that is higher than a level of expression in disease-free individuals, where metastatic cancer is implicated when claudin 3 or claudin 4 or both claudins 3 and 4 are expressed at or above said level that is higher than a level of expression in disease-free individuals.
A chimeric anticancer agent comprising
- an antibody that recognizes claudin-3 or claudin-4, or both;
- and
- a cytotoxic agent.
A chimeric anticancer agent comprising
- Clostridium perfringens enterotoxin or a fragment of Clostridium perfringens enterotoxin, and
- a matrix metalloprotease.
Clostridium perfringens enterotoxin truncated by 45 amino acids at an amino terminus.
Dependencies are inferred from the claim text.