Immunotherapeutic method of treating neoplastic conditions
The present invention relates generally to a method for detecting an aberrant cell, and more particularly an apoptotic cell, in a subject or in a biological sample from said subject, and agents useful for same. The presence of the aberrant cell or group of aberrant cells provides an indication of a particular disease or condition or a propensity for development of a disease or condition. More particularly, the present invention contemplates a method for detecting an apoptotic cell by detecting the presence of extranuclear nuclear molecules, in particular La, or a relative increase in extranuclear nuclear molecule levels. The present invention further provides a method for diagnosing or monitoring conditions characterized by aberrant, unwanted or otherwise inappropriate cellular apoptosis in a subject or in a biological sample from said subject by screening for up-regulation of extranuclear nuclear molecule levels in a cell or group of cells. The present invention provides diagnostic agents useful for detecting these molecules. Such diagnostic agents include immunointeractive molecules, such as antibodies.
1. A method of treating a neoplastic condition in a subject, comprising:
administering to said subject an effective amount of an immunointeractive molecule which binds to La-SS/B or antigenic determinant or epitope thereof, wherein said immunointeractive molecule is an antibody, a monoclonal antibody, a polyclonal antibody, a humanized antibody, a chimaeric antibody, a minibody, a single chain antibody, a deimmunised antibody, an Fv fragment, an Fab fragment, an Fab′ fragment, an F(ab′) 2 fragment, an (scFv-Fc) 2 fragment, a single chain Fv fragment, a disulphide-stabilised Fv fragment or a single variable region domain (dAb), and wherein said-immunointeractive molecule is linked, bound or otherwise associated with a proteinaceous or non-proteinaceous molecule which downregulates growth of tumor cells, for a time and under conditions sufficient to treat said neoplastic condition.
2. The method according to claim 1 , wherein said neoplastic condition is a central nervous system tumour, retinoblastoma, neuroblastoma or other paediatric tumour, head and neck cancer, breast and prostrate cancer, lung cancer, kidney cancer, oesophagogastric cancer, hepatocellular carcinoma, pancreaticobiliary neoplasia, colorectal cancer, cervical or anal cancer, uterine or other reproductive tract cancer, urinary tract cancer, germ cell tumour, ovarian cancer, carcinoma of unknown primary, human immunodeficiency associated malignancy, lymphoma, leukemia, malignant melanoma, sarcoma, endocrine tumour, mesothelioma or other pleural tumour, neuroendocrine tumour, or carcinoid tumour.
3. The method according to claim 2 , wherein said head and neck cancer is a squamous cell cancer, said lung cancer is a small or non-small lung cell cancer, said kidney cancer is a renal cell adenocarcinoma, said pancreatic reoplasma is an adenocarcinoma islet cell tumour, said germ cell tumour is testicular cancer or ovarian cancer, said ovarian cancer is an ovarian epithelial cancer, said human immunodeficiency associated malignancies is kaposis sarcoma, and said endocrine tumour is a tumour of the thyroid gland.
4. The method according to claim 2 , wherein said neoplasm is metastatic cancer.
5. The method according to claim 1 , wherein said condition is a tumour and wherein said proteinaceous or non-proteinaceous molecule is selected from the group consisting of:
(a) a cytokine;
(b) a chemokine;
(c) a macrophage, dendritic cell or T cell activator; and
(d) a toxin.
6. The method according to claim 5 , wherein said macrophage activator is N-formyl-methionyl-leucyl-phenylalanine or a bacterial lipopeptide.
7. The method according to claim 6 , wherein said bacterial lipopeptide is JBT2002.
8. The method according to claim 5 , wherein said toxin is a radioisotope.
9. The method according to claim 8 , wherein said radioisotope is an alpha particle emitter, a beta particle emitter or a gamma particle emitter.
10. The method according to claim 9 , wherein said alpha emitter is Tb-149 or Bi-213.
11. The method according to claim 5 , wherein said toxin is ricin, a prodrug or a biotherapeutic agent.
12. The method according to claim 11 , wherein said prodrug is an antibody-directed prodrug converting enzyme.
13. The method according to claim 11 , wherein said biotherapeutic agent is a catalytic antibody.
14. The method according to claim 1 wherein the deimmunised antibody is a humanised antibody.
15. The method according to any one of claims 1 , 2 , 3 , or 14 wherein said proteinaceous or non-proteinaceous molecule kills tumour cells.
16. The method according to any one of claims 1 , 2 , 3 or 14 wherein said mammal is a human.