Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Cancer cell or component thereof
Reexamination Certificate
1997-05-29
2002-01-15
Bansal, Geetha P. (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Cancer cell or component thereof
C424S184100, C435S242000, C435S242000, C435S242000, C435S243000, C435S070100, C435S404000, C514S002600, C514S008100, C514S012200, C530S350000, C530S351000, C530S395000, C530S806000
Reexamination Certificate
active
06338853
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to human vaccines, such as vaccines for protection against pathogenic microorganisms, e.g. bacterial infections and the like, and to human anti-cancer vaccines. More particularly, and in one special embodiment, this invention relates to the preparation of human anti-cancer vaccines useful for the prevention and/or treatment of cancer, such as melanoma, breast cancer, colon cancer, lung cancer and other such cancers.
For the treatment of cancer, it has been suggested to increase tumor protective immunity by active immunization to tumor antigens, see (1) the article by R. K. Oldham entitled “Biologicals and Biological Response Modifiers: Fourth Modality of Cancer Treatment”,
Cancer Treat Rep
(1984) :68:221-232, and (2) the article by M. J. Mastrangelo et al entitled “Current Condition and Prognosis of Tumor Immunotherapy: A Second Opinion”,
Cancer Treat Rep
(1984) :68:207-219. Unfortunately, this approach for the prevention and/or treatment of cancer has not been successful or completely satisfactory because of a number of problems, such as the absence in the vaccine of tumor antigens expressed by the tumor to be treated, poor characterization of the antigens in tumor vaccines, the contamination of vaccines by immunogenic but undesirable material, such as fetal calf serum (FCS) protein or transplantation antigens and additionally due to the antigenic heterogenicity of the cancer cells. Moreover, such tumor vaccines were often prepared from fresh tumor cells, the supply of which is limited so that the properties of the vaccines are not reproducible.
A clinical trial was conducted to evaluate the toxicity and immunogenicity in man of a partially purified, polyvalent, melanoma antigen vaccine and some success was indicated, see the abstract of the paper by J. C. Bystryn et al published by
The Society for Investigative Dermatology, Inc
. entitled “Phase 1 Trial of Specific Immunotherapy of melanoma with a Polyvalent Melanoma Antigen Vaccine.”
It is an object of this invention to provide an improved anti-cancer vaccine.
It is another object of this invention to provide a technique for the preparation of an improved anti-cancer vaccine.
It is another object of this invention to provide an immunotherapy for the prevention and/or treatment of human cancer.
Yet another object of this invention is to provide a technique for the production of reproducible anti-cancer vaccines.
Still another object of this invention is to provide a technique for the preparation of an anti-cancer vaccine useful when introduced into a patient to prevent and/or to treat cancer.
It is still another object of this invention to provide a technique for the preparation of vaccines for diseases caused by infectious cellular and/or subcellular organisms and/or viruses.
It is yet another object of this invention to provide a technique for the preparation of clinically or biologically important material shed from the surface of cells and the like.
How these and other objects of this invention are achieved will become apparent in the light of the accompanying disclosure. In at least one embodiment of the practices of this invention at least one of the foregoing objects will be achieved.
SUMMARY OF THE INVENTION
A human vaccine useful for the prevention and/or treatment of infections caused by pathogenic microorganisms, including viral, fungal, protozoal, amoebic and bacterial infections and the like, human cancer, including human melanoma, a skin cancer, human lung cancer, human breast cancer, human colon cancer and other human cancers is produced. For the production of a human cancer vaccine, the vaccine is produced by culturing human cancer cells, such as human melanoma cells, in a serum-free medium for the collection in the medium of cancer antigens, such as multiple melanoma associated antigens (MAAs). The vaccine produced from the shed material contains multiple cell surface antigens including tumor antigens and if prepared from cells adapted to and grown in a serum-free medium, is free of calf serum proteins. The use of bioreactors for the bulk culture of the cells and the like for vaccine production is particularly useful.
The vaccine is employed for the prevention and/or treatment of cancer in humans by administering the vaccine into the extremities of the patient a number of times a month and then once every few months thereafter for an extended period of time, such as 1-4 years, more or less. As indicated, the invention is applicable for the production of vaccines for the prevention and treatment of other cancers as well as for infectious diseases caused by bacteria, fungi, rickettsia, virus and other cellular and subcellular organisms.
DETAILED DESCRIPTION OF THE INVENTION
The practices of this invention are hereinafter described in some detail with respect to the production of a human melanoma antigen vaccine and the treatment of melanoma patients. As indicated hereinabove, however, the practices of this invention are also applicable to the production of a human lung cancer vaccine, a human breast cancer vaccine, a human colon cancer vaccine and other human cancer vaccines as well as vaccines for infectious diseases, particularly infectious diseases caused by bacteria, fungi and other microorganisms.
In the preparation of a human melanoma antigen vaccine in accordance with this invention the vaccine was prepared from material shed by four lines of human melanoma cells: HM31, HM34, HM49, and SR-Mel-28. The cells were selected on the basis of the cells expressing different patterns of cell surface melanoma antigens and adapted to and maintained in serum-free medium, see the article by J. P. Mather et al entitled “The Growth of Mouse Melanoma Cells in Hormone Supplemented Serum-Free Medium”,
Exp Cell Res
1979:120:191-200, for at least 8 weeks prior to use.
Antisera
A panel of eight murine monoclonal antibodies and two rabbit polyclonal melanoma antisera were used for MAA immunophenotyping. The antigens defined are listed in accompanying Table 1. The antigens defined by the murine and rabbit antisera are different, even though some may have similar molecular weights, as shown by variations in their distribution among melanomas (Table 3).
Vaccine Preparation
Melanoma cells were incubated at a concentration of 2×10
6
/ml serum-free RPMI 1640 medium. After 3 hours at 37° C., the medium was collected and the cells were removed by centrifugation at 2,000 g for 10 minutes, and larger particles were removed by recentrifugation at 12,000 g for 15 minutes. Equal volumes of medium from the four cell lines were pooled, concentrated 10-fold by vacuum ultrafiltration and made up to a final concentration. In some cases vaccines were prepared with further treatment including the addition of a non-ionic surfactant, e.g. 0.5% Nonidet P-40 (NP-40) and 0.02% sodium azide as a preservative, and then ultracentrifuged at 100,000 g for 90 minutes. The supernatant was dialyzed at 4° C. against normal saline with 0.02% sodium azide and made up to the desired protein concentration by the addition of normal saline, passed through a 0.1 um Millex Millipore filter to remove microorganisms; and 0.5 ml aliquots dispensed into sterile, pyrogen-free glass vials. The vials were stored at −70° C. until used.
A control vaccine was similarly prepared from a pool of normal peripheral leukocytes obtained from five normal individuals. Prior to use, the vaccine was tested for aerobic and anaerobic bacteria, fungi, and hepatitis antigen and also tested for mycoplasma by bisbenzamide DNA fluorochrome stain and for pyrogens by the limulus test. For MAA phenotyping, the vaccine was prepared from cells radioiodinated by the lactoperoxidase technique, see the article by J. C. Bystryn et al entitled “Identification and Solubilization of Iodinated Cell Surface Human Melanoma Associated Antigens”,
Int J Cancer
1977:20:165-172, and radiolabeled cells were lysed in 10 ml of 0.15 NP-40.
Assays
Protein concentration was measured by the Lowry method, see the article by O. H. Lowry et al entitle
Bansal Geetha P.
Cooper & Dunham LLP
Katz Robert D.
LandOfFree
Anti-cancer vaccine does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anti-cancer vaccine, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-cancer vaccine will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2839788