Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Structurally-modified antibody – immunoglobulin – or fragment...
Patent
1997-02-21
1999-06-15
Scheiner, Toni R.
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Structurally-modified antibody, immunoglobulin, or fragment...
4241331, 4241451, 4241541, 4241591, 4242771, 5303873, 5303883, 53038822, 53038823, A61K 39395, A61K 3942, C07K 1624
Patent
active
059119870
DESCRIPTION:
BRIEF SUMMARY
This is a national phase filing of the application No. PCT/EP95/00843, which was filed with the Patent Corporation Treaty on Mar. 7, 1995, and is entitled to priority of the German Patent Application P 44 07 538.3, filed Mar. 7, 1994.
I. FIELD OF THE INVENTION
The present invention relates to a bonding reagent, a process for the production thereof and a vaccine containing the bonding reagent.
II. BACKGROUND OF THE INVENTION
It is known that in the case of the active immunization the cells used often only show weak or no immunogenicity. This is found particularly when tumor cells are employed.
Experiments were made to increase the immunogenicity of cells. As in the use of oncolyzates obtained by Newcastle Disease Virus (referred to as NDV hereinafter), such experiments often failed to yield satisfactory results.
Thus, it is the object of this invention to provide a composition by which the immunogenicity of cells can be increased.
III. SUMMARY OF THE INVENTION
The present invention relates to a bonding reagent, which is characterized in that it comprises a first bonding component for a cell surface protein and a second bonding component for a costimulatorily acting molecule of an effector cell.
Furthermore, this invention concerns a process for the production of the bonding reagent as well as a vaccine containing the bonding reagent.
IV. BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a diagram of the expression plasmid pOPE51-.alpha.HN.
Abbreviations. Ap.sup.R : gene encoding ampicillin resistance; bp: base pairs, c-myc: sequence coding for an epitope recognized by mAk 9E10; Cys: nucleotides which code for an individual cysteine residue; (His).sub.5 : sequence coding for five C terminal histidine residues; IG: "intergenic" region of phage f1, leader: signal peptide sequence of the bacterial pectate lyase (pe1B leader); linker: sequence coding for (Gly.sub.4 Ser).sub.3 linking V.sub.H and V.sub.L ; ori: origin of the DNA replication for ColE1; P/O: lac operon promoter/operator; V.sub.H and V.sub.L : variable region of the heavy chain and light chain, respectively, of the anti-HN antibody.
FIG. 2 shows a diagram of the expression plasmid pOPE51-.alpha.CD28.
Abbreviations. Ap.sup.R : gene encoding ampicillin resistance; bp: base pairs; c-myc: sequence coding for an epitope which is recognized by mAk 9E10; Cys: nucleotides which code for an individual cysteine residue; (His).sub.5 : sequence coding for five C terminal histidine residues; IG: "intergenic" region of phage f1, leader: signal peptide sequence of the bacterial pectate lyase (pelB leader); linker: sequence coding for (Gly.sub.4 Ser).sub.3 linking V.sub.H and V.sub.L ; ori: origin of the DNA replication for ColE1; P/O: lac operon promoter/operator; V and V.sub.L : variable region of the heavy chain and light chain, respectively, of the anti-.alpha.CD28 antibody.
FIG. 3 shows a diagram of a bonding reagent according to the invention.
Abbreviations. anti HN: anti-HN antibody; anti CD28: anti-CD28 antibody; S=S: disulfide bridge.
V. DETAILED DESCRIPTION OF THE INVENTION
It is the objective of the subject invention to provide a composition by which the immunogenicity of cells can be increased.
According to the invention this is attained by providing a bonding reagent which is characterized in that it has a first bonding component for a cell surface protein and a second bonding component for a costimulatorily acting molecule of an effector cell.
The expression "first bonding component" comprises any compound which may bond to a cell surface protein, on the one hand, and to a second bonding component, on the other hand. The bond may be direct or indirect. Preferably, the compound is an antibody or a portion thereof which has a bonding domain. Such a portion is favorably a Fab', (Fab') .sub.2, F.sub.v or (F.sub.v) .sub.2 fragment. The F.sub.V fragment of an anti-hemagglutininneuraminidase antibody has proved to be especially favorable.
The expression "cell surface protein" comprises any molecule which may be present on a cell surface. It may b
REFERENCES:
Bohlen et al., 1993, "Cytolysis Of Leukemic B-Cells By T-Cells Activated Two Bispecifc Antibodies," Cancer Research 53: 4310-4314.
Bohlen et al., 1993, "Lysis Of Malignant B Cells From Patients With B-Chronic Lymphocytic Leukemia By Autologous T Cells Activated With CD3 .times. CD19 Bispecific Antibodies In Combination With Bivalent CD28 Antibodies," Blood 82:1803-1812.
Ertel et al., 1993, "Viral Hemagglutinin Augments Peptide-Specific Cytotxic T Cell Responses," European Journal of Immunology 23:2592-2596.
Fanger et al., 1992, "Bispecific Antibodies," Critical Reviews in Immunology 12:101-124.
Nishimura et al., 1992, "Human c-erbB-2 Proto-Oncogene Product As A Target For Bispecific-Antibody-Directed Adoptive Tumor Immunotherapy," International Journal of Cancer 50:800-804.
Schirrmacher, 1993, "Active Specific Immunotherapy--A New Modality Of Cancer Treatment Involving The Patient's Own Immune System," Onkologie 16:290-296.
Azuma et al., 1993, "B70 antigen is a second ligand for CTLA-4 and CD28," Nature 366: 76-79.
Dubel et al., 1993, "A family of vectors for surface display and production of antibodies," Gene 128:97-101.
Freeman et al., 1993, "Cloning of B7-2: A CTLA-4 Counter-Receptor That Costimulates Human T Cell Proliferation," Science 262:909-911.
Iorio et al., 1986, "Genetic Variation within a Neutralizing Domain on the Haemagglutinin-Neuraminidase Glycoprotein of Newcastle Disease Virus," J. gen. Virol. 67:1393-1403.
Kurucs et al., 1993, "A bacterially expressed single-chain Fv construct from the 2B4 T-cell receptor," Proc. Natl. Acad. Sci. USA 90:3830-3834.
Breitling Frank
Dubel Stefan
Gotter Stefanie
Haas Claudia
Khazaie Khashayarsha
Deutsches Krebsforschungszentrum Stiftung des Offentlichen Recht
Scheiner Toni R.
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