Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Cancer cell or component thereof
Reexamination Certificate
1999-01-15
2001-03-27
Huff, Sheela (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Cancer cell or component thereof
C424S184100
Reexamination Certificate
active
06207170
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is directed to the production of novel compositions, useful as vaccines for treating white blood cell (WBC) malignancies. The invention relates to a liposomal, patient-specific vaccine comprised of WBC membranes that may be formulated by adding other lipids and/or immunostimulators, thereby forming a novel membrane-proteoliposome (MP) structure.
Known vaccines typically utilize either purified antigen or attenuated pathogen as the immunogen. However, attenuated vaccines can actually cause the infection against which a person is being immunized. On the other hand, purified antigens may not induce a longterm immune response and sometimes induce no response at all. In contrast to the short-term immune response obtained by direct immunization with certain antigens, presentation of the antigen in the presence of liposomes can induce a long-term response which is essential for any effective vaccine.
Although typically formed from purified or partially purified lipids, liposomes may also be formed, at least in part, from cell membranes of malignant cells which contain potential antigens. Due to the presence of membrane associated antigens, these membranederived preparations may be used as malignancy-specific vaccines. Indeed, some types of membrane-derived preparations have been used as tumor specific antigens (TSA) to treat melanomas and murine SL2 lymphosarcoma. See Gershman et al., Vaccine Res. 3:83-92 (1994); Bergers et al., J. Confr. Rel. 29:317-27 (1994); Bergers et al., J. Liposome Res. 6:339-35 (1996). In these cases, the production of vaccine suffered from serious disadvantages. Namely, they required pooling culture adapted cells to achieve large amounts of the desired cell populations, use of whole &ggr;-irradiated tumor cells, detergent solubilization or butanol for crude extraction of tumor-associated antigens (TAA). See Gershman et al. (1994), supra; Abbas, et al., CELLULAR AND MOLECULAR IMMUNOLOGY, pp.372-73 (W. B. Saunders Company, Philadelphia 1994); Bergers et al. (1994), supra; LeGrue et al., J. Natl. Cancer Inst. 65:191-96 (1980). This approach, moreover, is not patient-specific.
The art is also aware of some vaccines directed to certain B cell malignancies. Typically, however, attempts at producing vaccines for B-cell lymphoma have relied on the costly and time consuming hybridoma technology. These methods depend on generating a hybridoma able to produce the tumor-specific immunoglobulin (Ig) in enough quantity to be then used as a vaccine. Kwak et al., Blood 76:2411-17 (1990); Kwak et al., N. Engl. J. Med. 327:1209-15 (1992). Known B-cell lymphoma vaccines employ Ig idiotype (Id) to generate anti-idiotype antibodies to B-cells. Levy et al., PCT/US94/08601 (Feb. 23, 1995); Levy et al., U.S. Pat. No. 4,816,249 (1989). Similarly, known melanoma vaccines involved harvesting cell surface antigens which are shed during culturing. Bystryn, U.S. Pat. No. 5,635,188 (1997); Bystryn, U.S. Pat. No. 5,194,384 (1993); Bystryn, U.S. Pat. No. 5,030,621 (1991).
There is, therefore, an unmet need in the art for improved liposome-based vaccines. A particular need exists for improved vaccines against white blood cell malignancies.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the invention to provide novel vaccine compositions that overcome the above-identified and other deficiencies in the art. According to this object of the invention, membrane-proteoliposomes (MPs) are provided which are malignancy-specific, patient-specific and are easily prepared. Thus, in one embodiment, MPs are provided which comprise the cell membrane of a white blood cell malignancy, at least one immunostimulator and at least one lipid, where the lipid may be added in the form of lipid powder, or preformed liposomes. Another embodiment of the invention provides novel vaccine formulations which comprise an MP comprising the cell membrane of a white blood cell and may include at least one immunostimulator.
It is yet another object of the invention to provide methods for preparing MPs and vaccines which also overcome the deficiencies in the art. According to this object of the invention, methods are disclosed that do not rely on harvesting the vaccine antigen, hybridoma production or other intermediate steps. The inventive methods comprise formulating a vaccine directly from isolated antigen-containing membranes from patients' own white blood cells (WBCs), thus rendering them highly effective and patient-specific.
REFERENCES:
patent: 4816249 (1989-03-01), Levy et al.
patent: 5030621 (1991-07-01), Bystryn
patent: 5194384 (1993-03-01), Bystryn
patent: 5635188 (1997-06-01), Bystryn
patent: 0 283 443 (1988-09-01), None
patent: WO 94/08601 (1994-04-01), None
patent: 97/29769 (1997-08-01), None
Zintl et al.; “Prerequisites and Possibilities of Immunotherapy In Acute Leukemia”; Apr. 15, 1976; pp. 227-231; XP002103820.
Neil Gershman, Dean Johnston and Jean-Claude Bystryn; Potentiation of Melanoma Vaccine Immunogenicity by Interleukin 2 Liposomes; Vaccine Research, vol. 3, No. 2, 1994; pp. 83-92.
J.J. Bergers, W. Den Otter and D.J.A. Crommelin; Vesicles for tumour-associated antigen presentation to induce protective immunity: preparation, characterization and enhancement of the immune response by immunomodulators;Journal of Controlled Release, 29 (1994) pp. 317-327.
Joep J. Bergers, Willem Den Otter and Daan J.A. Crommelin; Liposome-Based Cancer Vaccines; Journal of Liposome Research, 6(2), pp. 339-355 (1996).
Abul K. Abbas, Andrew H. Lichtman, M.D., Jordan S. Pober, M.D.; Cellular and Molecular Immunology; Saunders Text and Review Series; pp. 372-373, 1994.
Stephen J. LeGrue, Barry D. Kahan and Neal R. Pellis; Extraction of a Murine Tumor-Specific Transplantation Antigen With 1-Butanol. I. Partial Purification by Isoelectric Focusing; Jnci. vol. 65, No. 1, Jul. 1980; pp. 191-196.
Larry W. Kwak, Michael J. Campbel, Andrew D. Zelenetz, and Ronald Levy; Combined Syngeneic Bone Marrow Transplantation and Immunotherapy of a Murine B-Cell Lymphoma; Active Immunization With Tumor-Derived Idiotypic Immunoglobulin; Blood; vol. 76, No. 11 (Dec. 1, 1990); pp. 2411-2417.
Larry W. Kwak, M.D., Michael J. Campbell, Ph.D., Debra K. Czerwinski, B.S., Sarah Hart, B.S., Richard A. Miller, M.D., and Ronald Levy, M.D.; Induction of Immune Responses in Patients with B-Cell Lymphoma Against the Surface-Immunoglobulin Idiotype Expressed by Their Tumors; Induction of Immune Responses in B-Cell Lymphoma, vol. 327, No. 17; pp. 1209-1215, 1992.
Tamauchi et al. Enhancement of immunogenicity by incorporation of lipid A into liposomal model membranes and its application to membrane-associated antigens. Immunology 50:605-612, 1983.
Batenjany Michael M.
Boni Lawrence
Popescu Mircea C.
Robb Richard J.
Biomira U.S.A., Inc.
Foley & Lardner
Harris Alana M.
Huff Sheela
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