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FEMS Immunology and Medical Microbiology Mar 1994Polyclonal rabbit anti-idiotypic antibody (anti-Id) against the protective monoclonal antibody specific to the flagella of Clostridium chauvoei was produced, purified,...
Polyclonal rabbit anti-idiotypic antibody (anti-Id) against the protective monoclonal antibody specific to the flagella of Clostridium chauvoei was produced, purified, and characterized. Anti-Id inhibited the binding of its related monoclonal antibody to the flagellar antigen, suggesting that the anti-Id bore an internal image of the flagellar antigen. When mice were immunized with anti-Id intraperitoneally, the survival rate increased significantly, compared with mice immunized with normal rabbit IgG (P < 0.01), and specific anti-flagellar antibodies were induced.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Bacterial; Antibodies, Monoclonal; Clostridium; Clostridium Infections; Enzyme-Linked Immunosorbent Assay; Flagella; Immunization; Immunoglobulin M; Mice; Mice, Inbred Strains
PubMed: 8004054
DOI: 10.1111/j.1574-695X.1994.tb00441.x -
Immunology Letters Jun 1991Anti-idiotypic (anti-Id) antibodies were raised against two murine monoclonal antibodies (mAb 1/1 and mAb 2/1) which recognise two distinct and well-characterised...
Anti-idiotypic (anti-Id) antibodies were raised against two murine monoclonal antibodies (mAb 1/1 and mAb 2/1) which recognise two distinct and well-characterised epitopes on a 24-residue synthetic peptide representing part of the haemagglutinin (HA) of influenza virus. A monoclonal anti-Id antibody, specific for mAb 2/1, could bind to mAb 2/1 when the paratope of the latter was occupied with peptide, indicating that this anti-Id antibody is directed to a framework idiotope. In contrast, an anti-Id mAb derived from mAb 1/1-immunised mice was inhibited in its binding to Id by the parent peptide and also by the heptapeptide NVPEKQT which constitutes the epitope recognised by mAb 1/1. The small size of this synthetic peptide eliminates the possibility of significant steric inhibition in the system, and establishes that this mAb is a true paratope-directed anti-Id antibody. The interaction of this anti-Id mAb with the paratope of mAb 1/1 in the presence of a set of peptide homologues of the epitope was also examined. A peptide as short as 5 residues, which contains two of the three irreplaceable residues of the epitope, could inhibit binding between the two mAbs.
Topics: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Viral; Binding Sites, Antibody; Binding, Competitive; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Immunoglobulin G; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptides; Radioimmunoassay
PubMed: 1715846
DOI: 10.1016/0165-2478(91)90006-v -
Journal of Immunology (Baltimore, Md. :... Jun 1989We have targeted CD4+ cytotoxic Th (Th/c) lymphocytes to a B cell lymphoma, through the use of a bispecific antibody containing binding sites for both the CD3 complex on... (Comparative Study)
Comparative Study
We have targeted CD4+ cytotoxic Th (Th/c) lymphocytes to a B cell lymphoma, through the use of a bispecific antibody containing binding sites for both the CD3 complex on the Th/c and the Id on the surface Ig of the B lymphoma (anti-CD3-anti-Id). Cloned, keyhole limpet hemocyanin (KLH)-specific Th/c cells were nonspecifically activated by the anti-CD3-anti-Id conjugate to lyse the Id+ B lymphoma A20-HL. This cytotoxicity was not inhibited by antibodies to CD4 or LFA-1 alpha molecules. The anti-CD3-anti-Id conjugates also induced non-lytic Th clones to become cytotoxic, a function not elicited when these cells were activated specifically by Ag. We compare this model to our previously described system where we targeted the KLH-specific Th/c cells to the Id+ B lymphoma A20-HL via a conjugate consisting of KLH covalently linked to the anti-Id antibody (KLH-anti-Id). The mechanism involved processing and presentation of KLH by the A20-HL target. This Ag-specific cytotoxicity was MHC class II restricted and was inhibited by antibodies to the CD4 molecule. In both systems, activation of the Th/c cells resulted in bystander killing of tumor but not normal targets. These results may have important implications for the use of Th/c cells in tumor immunotherapy.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Specificity; Antigens, Differentiation, T-Lymphocyte; B-Lymphocytes; Binding, Competitive; CD3 Complex; Cell Line; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Immunologic; Hemocyanins; Immunoglobulin Idiotypes; Mice; Mice, Inbred BALB C; Phenotype; Receptors, Antigen, T-Cell; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Time Factors
PubMed: 2523940
DOI: No ID Found -
Cancer Research Apr 1995We have generated and characterized a murine monoclonal anti-idiotype (Id) antibody, designated 11D10, which biologically and antigenically mimics a distinct and...
We have generated and characterized a murine monoclonal anti-idiotype (Id) antibody, designated 11D10, which biologically and antigenically mimics a distinct and specific epitope of the high molecular weight human milk fat globule primarily expressed by human breast and some other tumor cells at high density. This epitope is identified by mAb BrE1, which was used as the immunizing antibody or Ab1 to generate the anti-Id (Ab2) 11D10. 11D10 induced antitumor immune responses across species barriers, i.e., in mice and rabbits. In preclinical studies, cynomolgus monkeys were immunized with 2 mg of either 11D10 or the isotype- and allotype-matched control Ab2 3H1 after precipitation with aluminum hydroxide. All monkeys developed high titers of antibodies against the immunizing mouse immunoglobulin. Immunization with 11D10 induced anti-anti-idiotype antibodies (Ab3) which reacted with breast cancer cell lines but not with control T-cell and melanoma cell lines. The Ab3 shared idiotypes with BrE1 (Ab1), as demonstrated by their ability to inhibit 11D10 binding to BrE1. The Ab3 obtained with 11D10 bound specifically to human milk fat globule antigen and competed with BrE1 for binding to breast cancer cell lines, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, Id-specific cellular immune responses were demonstrated in monkeys immunized with 11D10 by T-cell proliferation assays. These results indicate that aluminum hydroxide-precipitated anti-Id 11D10 can induce breast cancer-specific antibodies in nonhuman primates and can serve as a potential network antigen for breast cancer patients.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Neoplasm; Breast Neoplasms; Epitopes; Immunity, Cellular; Immunotherapy; Lactoglobulins; Macaca fascicularis; Milk, Human; Tumor Cells, Cultured
PubMed: 7533665
DOI: No ID Found -
Molecular Immunology Jun 1994A monoclonal antibody (mAb), designated PS-7.6, was previously shown to enhance the growth-promoting activity of porcine growth hormone (pGH) in an experimental... (Comparative Study)
Comparative Study
A monoclonal antibody (mAb), designated PS-7.6, was previously shown to enhance the growth-promoting activity of porcine growth hormone (pGH) in an experimental hypophysectomized (hypox) rat model. The long lasting effect of PS-7.6 was postulated to be a result of the induction of anti-idiotypic antibody (anti-id) in these treated animals. An attempt was made in this report to further explore this issue. It was demonstrated that mice following immunization with PS-7.6 were capable of producing anti-id in serum. The antibody titers of mice immunized with a mixture of PS-7.6 and pGH were much higher than that of those being immunized with PS-7.6 alone. A monoclonal anti-id, designated 2A6, was generated and found to recognize the intact PS-7.6 and its F(ab')2 fragment under non-reducing condition in Western analysis. However, it did not interact with reduced PS-7.6, suggesting the necessity of both H and L chains for the expression of a conformational idiotype. In radioimmunoassay, 2A6 competed with pGH for the binding to PS-7.6, but failed to do so with a control anti-pGH mAb recognizing a distinct pGH epitope from that of PS-7.6. Results from a biospecific interaction analysis which monitored the molecular interactions in a real-time fashion confirmed the facts that 2A6 specifically recognized the variable region of PS-7.6 and that the recognition was inhibited by the presence of pGH. Enzyme-linked immunosorbent assay provided further evidence to indicate that 2A6 bound to GH binding protein, i.e. the soluble GH receptor, and pGH prevented this interaction in a dose-dependent manner. The biological effect of 2A6 was evaluated in hypox rats and shown to promote the growth of these GH-deficient animals. Taken together, the present findings clearly demonstrate that 2A6 raised against a growth-enhancing anti-pGH mAb mimics pGH both conformationally and functionally.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Formation; Antibody Specificity; Binding, Competitive; Enzyme-Linked Immunosorbent Assay; Female; Growth; Growth Hormone; Mice; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Swine
PubMed: 8028599
DOI: 10.1016/0161-5890(94)90174-0 -
Biological & Pharmaceutical Bulletin Apr 1996We prepared an anti-idiotype (Id) antibody against leptospirosis. Serum from rabbit immunized with monoclonal antibody (MAb) LW2, which reacted to the main protective...
We prepared an anti-idiotype (Id) antibody against leptospirosis. Serum from rabbit immunized with monoclonal antibody (MAb) LW2, which reacted to the main protective antigen prepared from Leptospira interrogans serovar lai, inhibited agglutination of the organism by MAb LW2. The immune rabbit serum was applied to a column coupled with normal mouse IgG as a ligand (first column), and the unbound fraction eluted was applied to a column coupled with MAb LW2 as a ligand (second column). The bound fraction (anti-Id antibody) eluted from the second column inhibited the binding of MAb LW2 to sonicated leptospiral cells in ELISA. Mice produced antibodies against Leptospira by intraperitoneal immunization with the anti-Id antibody at doses of 2 mu g/mouse or more. Hamsters were protected by immunization with the anti-Id antibody at doses of 2 and 20 mu g/hamster from the lethal infection of Leptospira. This is the first report concerning the use of an anti-Id antibody against leptospirosis.
Topics: Agglutination; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antigens, Bacterial; Bacterial Vaccines; Cricetinae; Enzyme-Linked Immunosorbent Assay; Immunoglobulin Idiotypes; Leptospira interrogans; Leptospirosis; Male; Mesocricetus; Mice; Rabbits
PubMed: 8860969
DOI: 10.1248/bpb.19.613 -
PloS One 2008Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1....
Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1. Env-based immunogens inducing such a response could be a major component of future anti-HIV-1 strategies. In this proof-of-concept study we describe the generation of two anti-idiotype (AI) murine antibodies mimicking the CD4bs epitope. Sera were collected from long-term non-progressor patients to obtain CD4bs-directed IgG, through sequential purification steps. The purified IgG were then used as Fab fragments to immunize mice for hybridoma generation. Two hybridomas (P1 and P2), reacting only against the CD4bs-directed IgG, were identified and characterized. The P1 and P2 antibodies were shown to recognize the idiotype of the broadly neutralizing anti-CD4bs human mAb b12. Both P1 and P2 Fabs were able to induce a strong anti-gp120 response in rabbits. Moreover, the rabbits' sera were shown to neutralize two sensitive tier 1 strains of HIV-1 in an Env-pseudotype neutralization assay. In particular, 3/5 rabbits in the P1 group and 1/5 in the P2 group showed greater than 80% neutralizing activity against the HXB2 pseudovirus. Two rabbits also neutralized the pseudovirus HIV-MN. Overall, these data describe the first anti-idiotypic vaccine approach performed to generate antibodies to the CD4bs of the HIV-1 gp120. Although future studies will be necessary to improve strength and breadth of the elicited neutralizing response, this proof-of-concept study documents that immunogens designed on the idiotype of broadly neutralizing Abs are feasible and could help in the design of future anti-HIV strategies.
Topics: AIDS Vaccines; Animals; Antibodies, Anti-Idiotypic; Antibodies, Viral; Antibody Formation; CD4 Antigens; Epitopes; HIV Envelope Protein gp120; Humans; Mice; Molecular Mimicry; Rabbits
PubMed: 18923648
DOI: 10.1371/journal.pone.0003423 -
Molecular and Cellular Endocrinology Mar 1989Polyclonal anti-idiotypic antibodies were raised to three monoclonal antibodies to bovine anti-Müllerian hormone, and purified by affinity chromatography. All...
Polyclonal anti-idiotypic antibodies were raised to three monoclonal antibodies to bovine anti-Müllerian hormone, and purified by affinity chromatography. All anti-idiotypes inhibited binding of labelled anti-Müllerian hormone to the monoclonal antibody against which they were directed; in addition, the anti-idiotypes directed against a non-zoospecific monoclonal antibody inhibited binding of labelled anti-Müllerian hormone to a monoclonal antibody raised against human testicular AMH, indicating that the idiotype against which these anti-idiotypes are directed recognizes a conserved epitope on the anti-Müllerian hormone molecule. These anti-idiotypes, but not those directed against other monoclonals, exhibit hormone-like activity in a bioassay for anti-Müllerian activity, and we suggest that they may act as antibodies against the anti-Müllerian hormone receptor.
Topics: Animals; Anti-Mullerian Hormone; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Binding, Competitive; Cattle; Cross Reactions; Female; Glycoproteins; Growth Inhibitors; Humans; Immunoglobulin Idiotypes; Immunohistochemistry; Male; Mullerian Ducts; Rats; Testicular Hormones; Testis
PubMed: 2787251
DOI: 10.1016/0303-7207(89)90121-4 -
Expert Opinion on Biological Therapy 2016Racotumomab (originally known as 1E10 mAb) is an anti-idiotype murine IgG1 directed to membrane glycoconjugates expressed in aggressive solid tumors. It was developed as... (Review)
Review
INTRODUCTION
Racotumomab (originally known as 1E10 mAb) is an anti-idiotype murine IgG1 directed to membrane glycoconjugates expressed in aggressive solid tumors. It was developed as a mirror image of the idiotype of another antibody against N-glycolyl-containing molecules, such as the NeuGcGM3 ganglioside. After a successful phase II/III study, racotumomab formulated in alum was conditionally approved in Latin American countries as maintenance therapy for advanced non-small cell lung cancer.
AREAS COVERED
This review analyzes the biology of the target antigen, summarizes preclinical studies and discusses clinical trials in adults and the pediatric experience with racotumomab.
EXPERT OPINION
Proper patient selection and combination with chemotherapy, radiotherapy or checkpoint inhibitors appear to be critical issues to maximize the effects of racotumomab vaccination in lung cancer. In a recent phase I clinical trial in children with relapsed or resistant neuroectodermal malignancies, racotumomab was well tolerated and immunogenic, and its evaluation as immunotherapy for high-risk neuroblastoma is warranted.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Cancer Vaccines; Carcinoma, Non-Small-Cell Lung; Child; G(M3) Ganglioside; Humans; Lung Neoplasms
PubMed: 26903265
DOI: 10.1517/14712598.2016.1157579 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Aug 2010To compare the in vitro antitumor immune responses induced by bivalent bispecific anti-idiotype antibody G22-I50 and monovalent anti-idiotype antibody G22 and I50, and... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the in vitro antitumor immune responses induced by bivalent bispecific anti-idiotype antibody G22-I50 and monovalent anti-idiotype antibody G22 and I50, and explore its possible mechanism.
METHODS
Proteins G22-I50, G22, and I50 were induced and identified by Western blot and ELISA. Peripheral blood monoclear cells (PBMC) were isolated and stimulated with G22-I50, G22, and I50 anti-idiotype antibodies, respectively. MTT assay and LDH release test were employed to examine the proliferation and cytotoxicity of the PBMC. The levels of IFN-gamma, IL-2, and IL-4 in the supernatant were detected by ELISA and changes of T lymphocyte subsets were determined by flow cytometry.
RESULTS
Western blot showed that G22-I50, G22, and I50 had specific binding capabilities to FC2 (Ab1). The activities of G22-I50, G22, and I50 had recovered and these proteins could be used in the in vitro study. The proliferation and cytotoxicity of the PBMC stimulated with G22-I50 were significantly higher than those stimulated with G22 or I50. The level of IFN-gamma and IL-2 in the culture supernatant of the PBMC stimulated with G22-I50 was higher than that in the G22 or I50 group, but the level of IL-4 did not increase. Compared with the G22 or I50 group, the proportion of CD4(+) and CD8(+) T cells and CD4(+)/CD8(+) ratio significantly increased, and the proportion of CD4(+)CD25(+) T cells significantly decreased in the PBMC stimulated with G22-I50.
CONCLUSION
G22-I50 has more potent immunogenicity and would enhance specific antitumor effect which might relate to improving PBMC proliferation, inducing the secretion of Th1 type cytokines, activating CD8(+)T cells, and suppressing the expression of CD4(+)CD25(+) T cells.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Neoplasm; Antibody Specificity; CD8-Positive T-Lymphocytes; Humans; Nasopharyngeal Neoplasms; T-Lymphocytes, Regulatory; Th1 Cells
PubMed: 20818068
DOI: 10.3969/j.issn.1672-7347.2010.08.002