News Column

Patent Issued for Compositions for Immunotherapy and Uses

July 22, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- MacFarlane Burnet Institute for Medical Research and Public Health Ltd (Melbourne, AU) has been issued patent number 8771701, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also MacFarlane Burnet Institute for Medical Research and Public Health Ltd).

The patent's inventors are McKenzie, Ian F. C. (Brunswick, AU); Apostolopoulos, Vasso (St. Albans, AU); Pietersz, Geoffrey A. (Greensborough, AU).

This patent was filed on November 17, 2006 and was published online on July 8, 2014.

From the background information supplied by the inventors, news correspondents obtained the following quote: "Cancer is a major cause of death and severe trauma in modern society. Cancer afflicts the young, old, males, females and peoples of all races may contract cancer, although cancer in children is relatively rare, perhaps with the exception of childhood leukemia. In western society, cancer of the colon and lung cancer are major diseases. In women, breast cancer is the most common form of cancer.

"Many cancers are accompanied by overproduction of human mucin. Mucins are heavily glycosylated proteins (greater than about 100 kilodalton (kD) which are produced by many epithelial cells and tumors (Gendler et al., J. Biol. Chem, 263:12820-12823, 1988). Mucins found on cancer cells are different in some respects to those on normal epithelial cells, in that some mucins have a deficiency in their carbohydrate coat which leaves the protein core exposed (Harisch et al., J. Biol. Chem., 264:872-883, 1989). There are seven forms of known human mucin designated MUC1, MUC2, MUC3, MUC4, MUC5, MUC6 and MUC7 (Marjolijn et al., J. Biol. Chem., 265:5573-5578, 1990; Crocker et al., Br. J. Cancer, 55:651-652, 1987; Apostolopoulos et al., Crit. Rev. Immunol., 14:293-309, 1994; and Bobek et al., J. Biol. Chem., 268:20563-20569, 1993). MUC1 is the most ubiquitous. The various mucins all have very similar properties, that is, they are transmembrane glycoproteins, all having a variable number of repeated amino acid sequences, which have a high content of serine, threonine and proline. Overproduction of aberrantly glycosylated mucins (either non-glycosylated or a deficiency in glycosylation) is characteristic of tumors of the breast, ovary, pancreas, colon, lungs, prostate and other tumors of secretory tissue. The copy DNA (cDNA) sequences of the respective protein cores of the human mucins MUC1 to MUC7 have been cloned and characterized and have been found to contain highly repetitive central portions of varying numbers of repeats of particularly amino acid motifs (known as VNTR's). By way of example, MUC1 consists of unique amino and carboxyl terminal sequences separated by a highly repetitive central portion containing forty to eighty tandemly arranged copies or repeats of a twenty amino acid motif. The VNTR's of MUC1 through MUC7 are set forth below:

"TABLE-US-00001 MUC1 VNTR- SAPDTRPAPGSTAPPAHGVT (SEQ ID NO: 1) MUC2 VNTR- PTTTPISTTTMVTPTPTGTQT (SEQ ID NO: 2) MUC3 VNTR- HSTPSFTSSITTTETTS (SEQ ID NO: 3) MUC4 VNTR- TSSASTGHATPLPVTD (SEQ ID NO: 4) MUC5 VNTR- PTTSTTSA (494 base pair insert - eight amino acid tandem repeat) MUC6 VNTR- 169 amino acid repeat unit (SEQ ID NO: 5) MUC7 VNTR- TTAAPPTPPATTPAPPSSSAPPE (SEQ ID NO: 6)

"The repeated subunit of MUC6 comprises 169 amino acids, although at this time the amino acid sequence of this repeat unit has not been fully characterized. The MUC7 sequence has recently been published (Bobek et al., ibid.).

"Finn and colleagues have demonstrated that in the lymph nodes of patients with breast cancer (Barnd et al., Proc. Natl. Acad. Sci USA, 86:7159-7163, 1989; and Jerome et al., in Cell. Immunity and Immunotherapy of Cancer, pp. 321-328, 1990), cancer of the pancreas, ovary and other tumors, cytotoxic lymphocytes are present which react with human mucin. Antibodies to the MUC1 peptide can block the activity of these cytotoxic T lymphocytes on MUC1 and target cells (Barnd et al., ibid.; and Jerome et al., ibid.). Recently, cytotoxic lymphocytes to a murine lung cancer have also been described (Mandelboimo et al., Nature, 369:67-71, 1994).

"The surgery associated with tumor removal is traumatic to the patient, often disfiguring, and costly. Established chemotherapeutic and radiation procedures for tumor treatment which may be carried out in place of, or in conjunction with, surgical procedures are often debilitating and associated with severe side-effects. There is accordingly an urgent need for immunoregulatory compositions and methods for the prevention/treatment of tumors.

"There is an urgent need for new compositions and methods for the treatment of cancer. Similarly, there is a pressing need for alternative compositions and methods for the treatment of other disease states such as type I allergies, malaria, HIV, dental caries, flu, cholera, foot and mouth disease, meningitis, Leishmania infection, whooping cough, rabies, Streptococcus infection, respiratory infection, measles, Lyme disease, tuberculosis, bacterial meningitis, shingles, rubella, hepatitis, herpes, hepatitis A, polio, venereal disease/trachoma, hepatitis B, common cold, cervical cancer, meningitis/pneumonitis, chicken pox, small pox and pneumonia/PUO."

Supplementing the background information on this patent, NewsRx reporters also obtained the inventors' summary information for this patent: "The present invention provides an immunoregulatory composition that is capable of regulating a T lymphocyte (T cell) response in an animal, thereby treating or alleviating the occurrence of disease. The present invention is advantageous because it regulates T cell responses by delivering an antigen to the MHC class I pathway for presentation by class I molecules, thereby inducing cytotoxic T lymphocytes and T1 (i.e., TH1) cytokine production, e.g., IL-2, IL-12 and gamma interferon. The invention is particularly advantageous in that it regulates T cell responses by increasing the uptake of an antigen: carbohydrate polymer conjugate of the present invention by inducing receptors for mannose on cells capable of stimulating T cells reactive to the antigen of the conjugate. In addition, the invention is particularly advantageous in that it enables an antigen, for example a mucin:carbohydrate polymer conjugate of the present invention, to be administered to an animal in such a manner that binding of the antigen, e.g., mucin, by naturally occurring antibodies directed against or crossreactive with the antigen in the animal is avoided. Moreover, an immunoregulatory composition of the present invention possesses the advantage of being substantially non-toxic upon administration to animals, and as a consequence the compositions are well tolerated by animals.

"One embodiment of the present invention includes an immunoregulatory composition comprising isolated mannose receptor-bearing cells and a conjugate comprising an antigen and mannose including fully oxidized mannose and/or partially reduced mannose having aldehydes. Preferred antigens include tumor, viral, fungal, protozoal or bacterial antigens. Preferred oxidized mannose comprises a carbohydrate polymer with aldehydes.

"Another embodiment of the present invention includes a composition comprising an immunoregulatory mannose receptor-bearing cell population, the population can be derived by culturing mannose receptor-bearing cells under conditions effective to produce the immunoregulatory mannose receptor bearing cell population, the conditions comprising an antigen delivery medium. A preferred antigen delivery medium comprises a conjugate comprising an antigen and mannose including oxidized mannose and/or partially reduced mannose having aldehydes.

"Yet another embodiment of the present invention includes an immunoregulatory mannose receptor-bearing cell population, in which the immunoregulatory mannose receptor-bearing cell population can be derived by a method comprising: (a) culturing mannose receptor-bearing cells in vitro with one or more biological response modifiers to produce an enhanced mannose receptor-bearing cell population; and (b) incubating the enhanced mannose receptor-bearing cell population with a conjugate comprising an antigen and mannose including oxidized mannose and/or partially reduced mannose having aldehydes, to obtain the immunoregulatory mannose receptor-bearing cell population. Preferred biological response modifiers include cytokines and vitamins.

"The present invention also includes an antigen delivery vehicle, comprising an isolated mannose receptor-bearing cell and a conjugate comprising antigen and a carbohydrate polymer comprising mannose including fully oxidized mannose and/or partially reduced mannose having aldehydes. Preferred antigen includes mucin. The present invention also includes a method for obtaining a population comprising immunoregulatory mannose receptor-bearing cells, the method comprising culturing a population of cells enriched for mannose receptor-bearing cells under conditions effective to obtain immunoregulatory mannose receptor-bearing cells, the conditions comprising an antigen delivery medium. Preferably, the method includes incubating the population of cells enriched for mannose receptor-bearing cells in the presence of one or more biological response modifier prior to the step of culturing.

"Another embodiment of the present invention includes a method to induce an immune response comprising administering to a recipient animal an effective amount of an immunoregulatory composition comprising mannose receptor bearing cells and a conjugate comprising an antigen and mannose including fully oxidized mannose and/or partially reduced mannose having aldehydes.

"The invention also includes a method to induce an immune response to an antigen, comprising contacting an isolated mannose receptor-bearing cell with a conjugate comprising antigen and mannose including fully oxidized mannose and/or partially reduced mannose having aldehydes, and administering the contacted cell to an animal.

"Also included in the present invention is a method for delivering an antigen to an animal by administering to an animal a mannose receptor-bearing cell that has been contacted with a conjugate comprising an antigen and mannose including fully oxidized mannose and/or partially reduced mannose having aldehydes, in which the mannose receptor-bearing cell is capable of presenting the antigen to a T cell in such a manner that a response is elicited from the T cell.

"Yet another embodiment of the present invention is a compound comprising an antigen conjugated to a carbohydrate polymer comprising partially reduced carbohydrate having aldehyde groups."

For the URL and additional information on this patent, see: McKenzie, Ian F. C.; Apostolopoulos, Vasso; Pietersz, Geoffrey A.. Compositions for Immunotherapy and Uses. U.S. Patent Number 8771701, filed November 17, 2006, and published online on July 8, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8771701.PN.&OS=PN/8771701RS=PN/8771701

Keywords for this news article include: Peptides, Proteins, Aldehydes, Amino Acids, Lymphocytes, Organic Chemicals, Mononuclear Leukocytes, MacFarlane Burnet Institute for Medical Research and Public Health Ltd.

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Source: Life Science Weekly


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