Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Reexamination Certificate
1998-10-27
2001-11-06
Bansal, Geetha P. (Department: 1642)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
C424S130100, C424S184100, C424S085100, C424S277100
Reexamination Certificate
active
06312718
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to methods for inducing humoral and cellular immune responses against malignant B cells. In particular, this invention is directed to methods for producing an integrated immunologic response against tumor cells using antigens that are associated with a B-cell malignancy.
2. Background
One of the major goals of immunotherapy is to harness a patient's immune system against tumor cells or infectious organisms. With regard to cancer therapy, the objective is to direct the patient's immune system against tumor cells by targeting antigens that are associated with tumor cells, but not normal counterparts. These tumor associated antigens (TAAs) have been difficult to identify. Certain tumor cells express antigens that are normally not expressed, or expressed at very low levels, in adult life, although they are present during fetal development. One example of such oncofetal TAAs is &agr;-fetoprotein, which is expressed by liver cancer cells. Another oncofetal TAA is carcinoembryonic antigen (CEA), which is expressed in most adenocarcinomas of entodermally-derived digestive system epithelia, as well as in breast tumor cells and non-small-cell lung cancer cells. Thomas et al.,
Biochim. Biophys. Acta
1032: 177 (1990).
The administration of anti-idiotype antibodies (Ab2s) mimicking TAAs represents a promising approach to cancer immunotherapy. Goldenberg, Amer.
J. Med.
94: 297 (1993). Ab2s are antibodies directed against the variable regions of conventional antibodies (Ab1). Certain Ab2s (termed “Ab2&bgr;”, “anti-idiotype” or “internal-image” antibodies) can mimic the three- dimensional structure of the nominal antigen, and thus Ab2 and antigen can bind with the same regions of the Ab1-combining site. Jerne et al.,
EMBO J.
1: 243 (1982); Losman et al.,
Int. J. Cancer
46: 310 (1990); Losman et al.,
Proc. Nat'l Acad. Sci. USA
88: 3421 (1991); Losman et al., Int. J. Cancer 56: 580 (1994). Individuals immunized with Ab2B can develop anti-anti-antibodies (Ab3), some of which can bind the nominal antigen.
The antigen mimicry properties of anti-idiotype antibodies have led to the use of Ab2B as surrogate antigens (or idiotype vaccines), when the nominal antigen is not readily available or when the host is tolerant to the nominal antigen. In experimental systems, immunization with Ab2B mimicking certain TAA creates specific immunity to the TAA and protect against subsequent tumor growth. See, for example, Nepom et al.,
Proc. Nat'l Acad. Sci. USA
81: 2864 (1984); Raychaudhuri et al.,
J. Immunol.
139: 271 (1987). Similarly, anti-idiotype vaccines have been developed against infectious organisms, such as
Streptococcus pneumoniae
[McNamara et al.,
Science
226: 1325 (1984)], hepatitus B virus [Kennedy et al.,
Science
223: 930 (1984)],
Escherichia coli
K13 [Stein et al.,
J. Exp. Med.
160: 1001 (1984)],
Schistosomiasis mansoni
[Kresina et al.,
J. Clin. Invest.
83: 912 (1989)], and Moloney murine sarcoma virus [Powell et al.,
J. Immunol.
142: 1318 (1989)].
However, the usefulness of this approach is limited. Cancer patients receiving an anti-TAA of animal origin will usually produce antibodies to the Ab1 and these anti-immunoglobulin antibodies include Ab2. Herlyn et al.,
J. Immunol. Methods
85: 27 (1985); Traub et al.,
Cancer Res.
48: 4002 (1988). The anti-idiotype response also may include the generation of T cells (T2). Fagerberg et al.,
Cancer Immunol. Immunother.
37: 264 (1993). Moreover, Ab2 may subsequently induce a humoral and cellular anti-anti-idiotypic response, Ab3 and T3, respectively, which may recognize the same epitope as Ab1. Id. This is a problem because it can reduce the effectiveness of the immune response.
Thus, an opportunity exists to provide an approach to immunotherapy utilizing both humoral and cellular immune systems. The present methods to provoke an integrated response against tumor cells, particularly malignant B cells, is an initial result of this approach.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a vaccine and method of treatment by inducing humoral and cellular immune responses against malignant B cells, in particular lymphoma, chronic lymphocytic leukemia and multiple myeloma. The vaccine comprises a liposomal preparation that incorporates at least one B cell malignancy associated antigen, at least one cytokine, and at least one type of lipid molecule. This combination therefore provides a novel and more potent vaccine formulation for B cell malignancies. The B-cell malignancy-associated antigen is preferably derived from the patient to be treated and thus the vaccine will be directed against the patient's malignant B-cells.
Thus, in one embodiment, the invention provides a vaccine comprising a liposome preparation comprising (1) at least one B-cell malignancy-associated antigen; (2) IL-2, alone or in combination with at least one other cytokine; and (3) at least one type of lipid molecule.
In another embodiment, the B-cell malignancy-associated antigen comprises all or part of an antibody associated with or produced by a malignant B-cell. Such malignant B-cells include those associated with lymphoma, chronic lymphocytic leukemia and multiple myeloma. In a further embodiment, the vaccine of the invention additionally comprises a tumor-associated antigen that is not an antibody or antibody fragment. Examples of such additional TAAs include, e.g., MUC-1, Epstein Barr Virus (EBV) antigen or an antigen associated with Burkitt's lymphoma.
In an alternative embodiment, the vaccines of the invention additionally comprise normal B-cell antigens such as HLA antigens.
In another embodiment, the vaccine of the invention additionally comprises a another cytokine; examples of additional cytokines include M-CSF, GM-CSF and IFN-gamma.
The vaccines of the invention comprise at least one lipid molecule selected from the group consisting of phospholipid, cholesterol, and glycolipid and derivatives of these lipids. In a further embodiment, the vaccines of the invention also comprise a carrier protein, e.g., albumin.
In another embodiment, a method for inducing humoral and cellular immune responses against malignant B-cells in a mammal is provided, comprising administering to said mammal a vaccine comprising a liposome preparation comprising (1) at least one B-cell malignancy-associated antigen; (2) IL-2, alone or in combination with at least one other cytokine; and (3) at least one type of lipid molecule.
REFERENCES:
patent: 4036945 (1977-07-01), Haber
patent: 4331647 (1982-05-01), Goldenberg
Chan et al AIDS, 9:223-228 1995.*
George et al J. Immunol. 141:2168-2174, 1988.*
Epstein et al Clin. Exper. Immunol. 53:257-271, 1983.*
Gregoriadis J Drug Targeting 2(5): 351-356, 1994.*
Arthur et al J Virol. 69(5): 3117-3124, 1995.*
T.M. Allen et al., “Pharmacokinetics of stealth versus unconventional liposomes: effect of dose”, Biochimica et Biophysica Acta., 1068, (1991) pp. 133-141.
T.M. Allen et al., “Subcutaneous administration of liposomes: a comparison . . . routes of injection”, Biochimica et Biophysica Acta., 1150, (1993), pp. 9-16.
S.M. Andrew et al., “Purification and Fragmentation of Antibodies”, Current Protocols in Immuno. (1997) pp. 2.7.1-2.7.12.
M.G. Baines et al., “Purification of Immunoglobulin G (IgG)”, Methods in Molecular Biology, vol. 10, Immuno. Protocols, 1992, pp. 79-104.
I.A.J.M Bakker-Woudenberg et al., “Liposomes as Carriers of Antimicrobial Agents or . . . Treatment of Infections”, Eur. J. Clin. Microbiol. Infect. Dis., vol. 12, Supp. 1, 1993, pp. 61-67.
E. Claassen et al., “The Effect of Elimination of Macrophages on the Tissue Distribution . . . [3H]Thotrexate”, Biochema et Biophysica Acta, 802 (1984), pp. 428-434.
D. Colcher et al., “In Vivo Tumor Targeting of a Recombinant Single-Chain Antigen-Binding Protein”, J. Nat. Cancer Inst., vol. 82, No. 14, 7/90, pp. 1191-1197.
L. R. Coney et al., “Cloning of a Tumor-ass
Boni Larry
Kwak Larry
Ochoa Augusto C.
Popescu Mircea C.
Bansal Geetha P.
Biomira USA Inc.
Foley & Lardner
LandOfFree
Vaccine for B-cell malignancies does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vaccine for B-cell malignancies, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vaccine for B-cell malignancies will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2602265