Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1998-04-21
2004-01-06
Romeo, David S. (Department: 1647)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S328000, C435S372200, C435S320100, C435S462000, C435S463000, C435S461000, C435S455000, C435S456000, C435S458000, C536S023400, C536S023500, C536S024100, C530S387300, C530S351000
Reexamination Certificate
active
06673573
ABSTRACT:
The present invention relates to a vector for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells, a method for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells, uses of said vector as well as malignant B cells containing said vector.
BACKGROUND OF THE INVENTION
The immunoglobulin idiotype expressed on B cell lymphomas is a tumor-specific antigen which however shows a low immunogenicity in the host bearing the tumor. Several approaches have been evaluated to induce an immune reaction against the idiotype. I. a., the idiotype has been coupled to GM-CSF to be used as a soluble protein for the vaccination of mice (Nature 362, 755-758, 1993). GM-CSF is able to recruit professional antigen-presenting cells and leads to an effective presentation of the idiotype and, thus, to the activation of T cells. This approach bears the disadvantage that the immunoglobulin V genes of the lymphoma have to be cloned and the fusion protein has to be produced in vitro and purified. Therefore, this would require in a clinical situation to prepare individual vaccines for each patient.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide novel vectors which may be employed universally in patients without need to prepare individual vaccines.
This object has been solved according to the invention by means of a vector for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells at least containing operably linked to each other
(a) a region of at least 1.5 kb which is homologous to a region of the &mgr; intron the &kgr; intron and which optionally contains or lacks or contains a non-functional C
&mgr;
or C
78
enhancer;
(b) at least one DNA sequence encoding a domain of an immunoglobulin or a part thereof;
(c) a DNA sequence encoding a cytskine; and
(d) a marker selectable in eukaryotic B cells which optionally contains an enhancer or lacks a functional enhancer region wherein following integration the expression of this marker is controlled by the cellular C
&mgr;
or C
&kgr;
enhancer.
Preferred embodiments of the invention become obvious from the dependent claims, the following Description as well as the Example.
REFERENCES:
patent: 5202238 (1993-04-01), Fell, Jr. et al.
patent: 44 06 512 (1995-02-01), None
patent: 195 41 450 (1997-05-01), None
patent: WO 94/04670 (1994-03-01), None
Tao et al. Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature Apr. 22, 1993;362(6422):755-8.*
Mocikat et al. Unaltered immunoglobulin expression in hybridoma cells modified by targeting of the heavy chain locus an integration vector. Immunology Jan. 1995; 84(1):159-63.*
Kardinal et al. Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exhange induced by a universal gene replacement vector. Immunology Nov. 1996; 89(3):309-15.*
Taylor-Papadimitriou et al. Fusion potential for vaccines. Nature Mar./Apr. 22, 1993;362(6422):695.*
Stevenson et al. A genetic approach to idiotypic vaccination for B cell lymphoma. Annals of the New York Academy of Sciences, (Nov. 27, 1995) 772 212-26.*
Kwak et al. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Engl J Med Oct. 22, 1992;327(17):1209-15.*
Parmiani et al. Cytokine gene transduction in the immunotherapy of cancer. Adv Pharmacol 1997;40:259-307.*
Terness et al. Idiotypic vaccine for treatment of human B-cell lymphoma. Construction of IgG variable regions from single malignant B cells. Human Immunology, (Aug.-Sep. 1997) 56 (1-2) 17-27.*
Kimball, John W. Introduction to immunology. Macmillan, New York. 1983, pp. 27-30.*
Lang et al. Replacement-like recombination induced by an integration vector with a murine homology flank at the immunoglobulin heavy-chain locus in mouse and rat hybridoma cells. Mol Gen Genet Mar. 1994;242(5):528-38.*
Dranoff et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A. Apr. 15, 1993;90(8):3539-43.*
Kardinal et al. Integration vectors for antibody chimerization by homologous recombination in hybridoma cells. Eur J Immunol Mar. 1995;25(3):792-7.
GSF-Forschungszentrum fur Umwelt und Gesundheit
Romeo David S.
Townsend and Townsend / and Crew LLP
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