Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Reexamination Certificate
2001-07-26
2004-07-20
Ungar, Susan (Department: 1642)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
C424S133100, C424S142100, C424S155100, C424S185100, C530S387100, C530S300000
Reexamination Certificate
active
06764680
ABSTRACT:
FIELD OF THE INVENTION
The invention is concerned with methods for in vivo immunotherapy of cancers associated with production of human chorionic gonadotropin (hCG) by administering a human anti-hCG monoclonal antibody and/or an hCG immunogenic peptide vaccine. The invention further relates to methods and devices for monitoring and adjusting the treatment regimen of patients, based on the results of an evaluation of the immune response to the 37 mer C-terminal fragment of hCG (hCG-CTP37) and immunogenic fragments thereof.
References
Abbas, A K, et al., Eds.,
Cellular and Molecular Immunology
, 3
rd
edition. W B Saunders Co., 394-405 (1997)
Acevedo, et al.,
Cancer
69:1829-1842 (1992)
Acevedo, et al,
Cancer Detect. Prev
. 1(Suppl.):447-287 (1987)
Braunstein, G D, In: IMMUNODAIGNOSIS OF CANCER, Herberman, R B and Mercer, D W, Eds, Marcel Dekker, Inc., New York, pages 673-701 (1990)
Dirnhofer, et al.,
Hum Pathol April;
29(4):377-82 (1998)
Fiddes, J. C. and Goodman, H. M. Nature, 281: 351-356 (1979)
Fiddes, J. C. and Goodman, H. M., Nature, 286: 684-687 (1980)
Fife, K and Bower, M,
Br. J Cancer
73:1317-1322 (1996)
Hudson, D., J. Org. Chem. 53:617-624, (1988)
Lee, A. C. J., et al., Mol. Immunol., 17:749 (1980)
Lee, et al., Mol Immunol 17:749-756, (1980)
Triozzi P L, and Stevens V C, Oncol Rep 6(1):7-17, 1999
Triozzi P L, et al., Clin Cancer Res 3(12 Pt 1): 2355-62, 1997
BACKGROUND OF THE INVENTION
Vaccination is a means for preparing the immune system to reduce disease symptoms, prevent horizontal transmission of infectious agents and reduce disease mortality. It is well known that the immune system of a subject will generate an immune response to foreign antigens. It is also known to confer immunity on an animal by administering an antibody formed elsewhere (i.e. passive immunization).
Standard vaccines include the administration of carbohydrates, peptides, polypeptides, and glycosylated polypeptides against which an immune response is desired (active immunization). Alternatives to vaccine administration include the administration of pre-formed antibodies to one or more peptide or polypeptides (passive immunization). Although polyclonal and monoclonal antibodies are readily produced by routine techniques, until recently, production and purification of safe antibody compositions has been relatively expensive and time consuming.
Historically, there have been serious limitations to the use of passive immunization procedures for human therapy. These limitations are most evident in the treatment of chronic diseases such as cancer due to the cost of antibody production and the requirement for prolonged administration of these antibodies. Additional difficulties are encountered when the immunogen is a soluble protein or an endogenous protein not normally recognized by the immune system of the subject.
Certain cancers are highly resistant to attack by the immune system of a host, even though in theory the host should mount an immune response against the cancer. It is believed that this resistance is due to the ability of the cancer to interfere with the normal immune response to the cancer cells, thereby allowing them to grow and proliferate.
Normally, Chorionic gonadotropin (CG), e.g. human chorionic gonadotropin (hCG), is secreted by cells of the human placenta and blastocyst. However, many human cancers produce and retain and/or secrete hCG at some point during carcinogenesis. hCG has been detected in the membranes of a variety of human cancer cell lines (Acevedo, et al., 1992), and in the serum of cancer patients (Braunstein, 1990). In fact, the hCG beta subunit C-terminal peptide (CTP) is highly expressed by a variety of cancers, and immunization with this construct has demonstrated antitumor activity in preclinical studies (Acevedo, et al., 1992; Acevedo, et al., 1987)).
For example, it has been demonstrated that hCG and/or its subunits are made by human lung cancer cells and that the hCG polypeptide or portions of it act as autocrine growth promoters for the tumor cells. (See, e.g., Rivera et al., 1989.) Additional references also describe that the active production of anti-hCG antibodies in tumor-bearing animals can result from administration of an hCG vaccine. (See, e.g., U.S. Pat. Nos. 5,762,931 and 4,780,312.).
Several biological activities associated with the ability of cancer cells to proliferate have been attributed to hCG including; (1) a link to tumor anergy (the lack of the immune response to tumors), (2) enhancement of tumor blood supply, and (3) the observation that hCG acts as a growth stimulatory factor for many cancer cells.
Epidemiological surveys indicate that human lung cancers are often associated with synthesis of hormones, predominantly human chorionic gonadotropin (hCG). Increased circulating levels of hCG and its subunits are often used as biochemical markers for malignancy, and decreased levels of hCG used as markers for successful surgery in human lung tumors. Free and/or tumor-associated &bgr;-hCG has been detected in bladder, pancreatic, cervical, colorectal, lung, pancreatic, esophageal breast, gastric, prostate, ovarian, uterine, cervical, and endometrial cancers, in addition to a majority of patients with germ cell tumors. (See, e.g., Dirnhofer, et al., 1998; Triozzi P L and Stevens V C, 1999). hCG and other gonadotropic hormones have also been associated with Kaposi's Sarcoma (K S, Fife, K and Bower, M, 1996).
Colorectal cancer is a disease that kills nearly half of those afflicted within 5 years of initial diagnosis and approximately one in 17 Americans develop colorectal cancer during their lifetime. Surgical intervention is not an option for most patients with advanced metastatic colorectal cancer. Initial chemotherapy with fluorouracil (5-FU) and leucovorin has become the standard for patients with stage III colon cancer (NIH Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer.
JAMA
264: 1444-1450, 1990; Goldberg R M and Erlichman C.
Oncology
12: 59-63, 1998). Therapy for patients with 5-FU-refractory advanced colorectal cancer is currently irinotecan (Van Cutsem E and Blijham G H.
Semin Oncol
26:. 13-20, 1999 and Cunningham D et al.
Lancet
352: 1413-1418, 1998). Multiple new approaches to the treatment of advanced colorectal cancer include: (a) new drugs such as oxaplatin, capecitabine, uracil/tegafur (UFT), (Punt C J.,
Cancer
1998; 15: 679-689, 1998); (b) passive immunotherapy using a monoclonal antibody, 17-1A (Punt C J., 1998); and (c) several approaches to active specific immunotherapy (ASI) with one or more cancer-associated antigens (Goydos J S et al.
J Sur Res
1996; 63: 298-304 and Vermorken, J B et al.
Lancet
1999; 353: 345-350).
Several Ohio State patents to Stevens, e.g., U.S. Pat. Nos. 4,767,842, 4,855,285, 5,817,753 and 5,698,201, expressly incorporated by reference herein, disclose the use of a beta-hCG/tetanus toxoid modified peptide as an anti-cancer strategy based on antibody production against hCG by the host.
Although various research efforts are directed to improved methods for treatment of hCG-expressing cancers, there remains a need for an effective and safe method for reducing or eliminating the level of circulating CG and cell-associated CG in cancer patients with CG-expressing tumors.
SUMMARY OF THE INVENTION
It is therefore a general object of the invention to provide methods for immunotherapy of cancers which express human chorionic gonadotropin (hCG), or an immunogenic epitope thereof.
The invention relates to methods of eliciting an immune response against hCG by administering an hCG immunogenic peptide vaccine composition to a subject, particularly a human cancer patient, as a means to diminish, prevent the spread of, and/or progression of cancer.
The invention also relates to a human monoclonal antibody composition specifically immunoreactive with a 21 mer N-terminal fragment of hCG-CTP37 (hCG-CTP21, SEQ ID NO:4) alone, or in combination with a human monoclonal antibody specifically immunoreactive with a 16 mer C-terminal fragment of hCG-CTP37 (hCG-CTP16, SEQ I
AVI BioPharma Inc.
Davis Minh-Tam
Perkins Coie LLP
Ungar Susan
LandOfFree
Combined approach to treatment of cancer with hCG vaccines does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Combined approach to treatment of cancer with hCG vaccines, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Combined approach to treatment of cancer with hCG vaccines will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3251326