Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex
Patent
1995-04-14
2000-08-08
Chan, Christina Y.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Conjugate or complex
424 851, 424 852, 4241801, 530351, 5303873, A61K 39385
Patent
active
060998466
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The invention relates to the field of modulating B cell lymphoma tumor growth using immunological methods. More specifically, the invention concerns use of immunological constructs to confer resistance to B cell lymphoma tumors, and to enhance immune response.
BACKGROUND ART
Malignant tumors often express characteristic antigens or "markers" which offer a mechanism for tumor prevention, resistance or treatment. The antigens which are characteristic of the tumor may be purified and formulated into vaccines. This may stimulate an antibody response and a cellular immune response which are helpful in controlling tumor growth. At a minimum, the antibodies raised by these antigens can be used as detection tools to monitor the level of tumor marker in the host to track the course of the disease or the effectiveness of treatment.
It is well known that the immunogenicity of antigens can be enhanced by coupling these hapten-bearing moieties to carriers. A variety of carriers are routinely used, such as keyhole limpet hemocyanin and various serum albumins. It is also understood that certain cytokines, such as GM-CSF, have the capacity to enhance primary antibody responses to antigens (Morrissey, P. J., et al, J Immunol (1987) 139: 1113-1119).
The immune response-enhancing ability of a cytokine, when coupled to a viral antigen, has been shown by Hinuma, S., et al, FEBS (1991) 288: 138-142. In this work, interleukin-2 was coupled to a herpes simplex virus type I glycoprotein by generating a fusion protein consisting of the glycoprotein D and human IL-2. The conjugate was shown to induce high antibody responses and cell-mediated immunity to HSV-I in mice.
It has now been found that B cell lymphoma tumor-associated antigens can be coupled to immune response-enhancing cytokines, such as GM-CSF, IL-2 and IL-4, to produce an immune response to the tumor antigen and enhance the ability of the host to resist tumor growth associated with the antigen.
DISCLOSURE OF THE INVENTION
The invention provides compositions and methods for the modulation of B cell lymphoma tumor growth where the tumor is characterized by an associated antigen carrying an epitope which is characteristic of the tumor. The immunogenicity of preparations of the antigen used to raise antibodies and stimulate an immune response can be enhanced by coupling the antigen to an appropriate cytokine. The conjugate is superior in effect to the antigen coupled to conventional immunogenic carriers.
In one aspect, the invention is directed to an immunocomplex, which complex comprises a B cell lymphoma tumor-associated antigen covalently coupled to an immune-enhancing cytokine. The complex may be obtained by generating the antigen and the cytokine as a fusion protein using recombinant techniques; thus, in another aspect, the invention is directed to recombinant materials and methods for production of such fusion proteins. In still other aspects, the invention is directed to pharmaceutical compositions and vaccines containing the immunogenic complexes of the invention and to methods of conferring antitumor immunity using these complexes. In still other aspects, the invention is directed to antibodies generated by immunization with the complexes of the invention and to antibodies immunospecific to the conjugates. The invention is also directed to methods to confer immunity by administering polyclonal or monoclonal preparations of antibodies generated by the conjugates.
It has also been found that the immune-enhancing cytokine activity is improved by extending or coupling the cytokine to an additional moiety. Accordingly, in another aspect, the invention is directed to enhancing the activity of a cytokine by coupling to an additional moiety.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A shows diagrammatically the construction of expression vectors for a B cell lymphoma tumor antigen Ig heavy chain coupled to murine GM-CSF;
FIG. 1B shows diagrammatically the construction of an expression vector for the light chain of this tumor-associated antigen.
FIG.
REFERENCES:
patent: 5281699 (1994-01-01), Chang
Morrissey, P.J., et al., "Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen presenting cells" J. Immunol. (1987) 139:1113-1119.
Hinuma, S., et al., "A novel strategy for converting recombinant viral protein into high immunogenic antigen" FEBS Letters (1991) 288:138-142.
Taylor-Papadimitriou, J., et al., "Fusion potential for vaccines" Nature (1993) 362:695.
Ahmad, A., et al., "Recombinant targeted proteins for biotherapy" Mol. Biother. (1990) 2:67-73.
Campbell, M.J., et al., "Immunotherapy of established murine B cell lymphoma. Combination of idiotype immunization and cyclophosphadine " J. Immunol. (1988) 141:3227-3233.
Campbell, M.J., et al., "Idiotype vaccination against murine B cell lymphoma" J. Immunol. (1990) 145:1029-1036.
Gillies, S.D. et al., "Biological activity and in vivo clearance of antitumor antibody/cytokine fusion proteins" Bioconjugate Chem. (1993) 4:230-235.
Kaminski, M.S., et al., "Idiotype vaccination against murine B cell lymphoma. Inhibition of tumor immunity by free idiotype protein" J. Immunol. (1987) 138:1289-1296.
Kwak, L.W., et al., "Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors" New Engl. J. Med. (1992) 327:1209-1215.
Osband, M.E. et al., "Problems in the investigational study and clinical use of cancer immunotherapy" Immunol. Today (1990) 11:193-195.
Roitt et al., Immunology 3rd Edition, Mosby Publications, Jan. 1993.
Kuby. Immunology. W.H. Freeman and Company. New York pp. 248,257-258, Jan. 1992.
Levy Ronald
Tao Mi-Hua
Chan Christina Y.
Nolan Patrick J.
The Board of Trustees of the Leland Stanford Junior University
LandOfFree
Enhancement of B cell lymphoma and tumor resistance using idioty does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Enhancement of B cell lymphoma and tumor resistance using idioty, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Enhancement of B cell lymphoma and tumor resistance using idioty will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1147732