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Expert Opinion on Biological Therapy Dec 2002The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumour immunity is one of several promising immunologic approaches to the therapy of cancer.... (Review)
Review
The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumour immunity is one of several promising immunologic approaches to the therapy of cancer. Extensive studies in animal tumour models have demonstrated the efficacy of anti-Id vaccines in preventing tumour growth and curing mice with established tumours. A number of monoclonal anti-Id antibodies that mimic distinct human tumour-associated antigens (TAAs) have been developed and tested in the clinic, and demonstrate encouraging results. In general, the antigen mimicry by anti-Id antibodies has reflected structural homology in the majority of the cases, and amino acid sequence homology in a few of them. The greatest challenge of immunotherapy by means of anti-Id vaccines is to identify the optimal anti-Id antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses. Although several clinical studies have shown enhanced survival of patients receiving anti-Id vaccines, the efficacy of these vaccines will depend on the results of several randomised Phase III clinical trials that are currently planned or ongoing.
Topics: Animals; Antibodies, Anti-Idiotypic; Cancer Vaccines; Disease Models, Animal; Humans; Immunotherapy, Active; Mice; Neoplasms
PubMed: 12517266
DOI: 10.1517/14712598.2.8.869 -
Frontiers in Immunology 2024The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype...
The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen.
Topics: Humans; Influenza A virus; Antibodies, Viral; Antibodies, Neutralizing; Antibodies, Anti-Idiotypic; Hemagglutinin Glycoproteins, Influenza Virus; Influenza, Human; Animals; Immunoglobulin Heavy Chains
PubMed: 38873606
DOI: 10.3389/fimmu.2024.1399960 -
Drugs of Today (Barcelona, Spain : 1998) Apr 2014Racotumomab is a murine gamma-type anti-idiotype monoclonal antibody that specifically induces an antibody response against Neu-glycolyl GM3 ganglioside (NeuGcGM3),... (Review)
Review
Racotumomab is a murine gamma-type anti-idiotype monoclonal antibody that specifically induces an antibody response against Neu-glycolyl GM3 ganglioside (NeuGcGM3), which is overexpressed in several solid tumors. It is adjuvanted with aluminum hydroxide for intradermal administration as a cancer vaccine (racotumomab-Alum, known commercially as Vaxira®). Racotumomab is currently being evaluated for a number of cancer indications, including melanoma, breast and lung cancer. In early clinical trials, racotumomab demonstrated high immunogenicity and low toxicity and it advanced to further clinical testing as a treatment for patients with non-small cell lung cancer (NSCLC). On the basis of promising results in a phase II/III study, racotumomab was launched in 2013 in Cuba and Argentina as an intradermal injection for the treatment of patients with advanced stage NSCLC.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Cancer Vaccines; Carcinoma, Non-Small-Cell Lung; G(M3) Ganglioside; Humans; Lung Neoplasms; Neoplasms
PubMed: 24918647
DOI: 10.1358/dot.2014.50.4.2116670 -
Toxins Dec 2020The use of synthetic antibody libraries and phage displays provides an efficient and robust method for the generation of antibodies against a wide range of targets with...
The use of synthetic antibody libraries and phage displays provides an efficient and robust method for the generation of antibodies against a wide range of targets with highly specific binding properties. As the in vitro selection conditions can be easily controlled, these methods enable the rapid generation of binders against difficult targets such as toxins and haptens. In this study, we used deoxynivalenol mycotoxin as a target to generate anti-idiotype-antibodies with unique binding properties from synthetic antibody libraries. The binding of the selected anti-idiotype antibodies can be efficiently inhibited with the addition of free isoforms of deoxynivalenol. The antibody was consecutively used to develop deoxynivalenol-specific ELISA and TRF-immunoassays, which can detect deoxynivalenol and two of the most common metabolic isoforms in the range of 78-115 ng/mL.
Topics: Antibodies, Anti-Idiotypic; Cell Surface Display Techniques; Immunoassay; Mycotoxins
PubMed: 33379255
DOI: 10.3390/toxins13010018 -
Journal of Basic and Clinical... Nov 2022Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The... (Review)
Review
Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The idiotype based hypothesis is discussed in this paper in order to produce effective anti-idiotype vaccinations. Polyclonal anti-idiotype reagents have been shown to be more successful in animal models, and a better understanding of the immune response in humans supports the idea that polyclonal anti-idiotype vaccines will be more effective than monoclonal-based anti-idiotype vaccines. This innovative approach can be used to produce therapeutic antibodies in a Biotech-standard manner. The idiotype network has been tweaked in the lab to provide protection against a variety of microbiological diseases. Antibodies to image-idiotype antigens, both internal and non-internal, can elicit unique immune responses to antigens. The current outbreak of severe acute respiratory syndrome 2 (SARS-2) has presented a fantastic chance to use idiotype/anti-idiotype antibodies as a protective regimen, which might be used to treat COVID-19 patients. The development of various effective vaccinations has been crucial in the pandemic's management, but their effectiveness has been limited. In certain healthy people, the development of viral variations and vaccinations can be linked to rare off-target or hazardous effects, such as allergic responses, myocarditis and immune-mediated thrombosis and thrombocytopenia. Many of these occurrences are most likely immune-mediated. The current analysis reveals successful idiotype/anti-idiotype antibody uses in a variety of viral illnesses, emphazising their importance in the COVID-19 pandemic.
Topics: Humans; Animals; COVID-19; Antibodies, Monoclonal; Pandemics; Immunoglobulin Idiotypes; Vaccines; Antibodies, Anti-Idiotypic
PubMed: 36279146
DOI: 10.1515/jbcpp-2022-0123 -
Survey of Immunologic Research 1982
Review
Topics: Animals; Antibodies, Anti-Idiotypic; Antibody-Producing Cells; B-Lymphocytes; Binding Sites, Antibody; Binding, Competitive; Cell Differentiation; Cross Reactions; Immunoglobulin Idiotypes; Lymphocyte Activation; Mice; Nitrophenols; Phenylacetates; Phosphorylcholine; Polysaccharides, Bacterial; T-Lymphocytes; p-Azobenzenearsonate
PubMed: 6764838
DOI: 10.1007/BF02918336 -
Cancer Immunology, Immunotherapy : CII Jun 2013Immunotherapy targeting disialoganglioside GD(2) emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here,...
PURPOSE
Immunotherapy targeting disialoganglioside GD(2) emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the induction of a GD(2)-specific immune response with ganglidiomab, a new anti-idiotype antibody to anti-GD(2) antibodies of the 14.18 family.
EXPERIMENTAL DESIGN AND RESULTS
Ganglidiomab was generated following immunization of Balb/c mice with 14G2a, and splenocytes were harvested to generate hybridoma cells. Clones were screened by ELISA for mouse antibody binding to hu14.18. One positive clone was selected to purify and characterize the secreted IgG protein (κ, IgG(1)). This antibody bound to anti-GD(2) antibodies 14G2a, ch14.18/CHO, hu14.18, and to immunocytokines ch14.18-IL2 and hu14.18-IL2 as well as to NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding of these anti-GD(2) antibodies to the nominal antigen GD(2) as well as GD(2)-specific lysis of neuroblastoma cells by NK-92-scFv(ch14.18)-zeta cells was competitively inhibited by ganglidiomab, proving GD(2) surrogate function and anti-idiotype characteristics. The dissociation constants of ganglidiomab from anti-GD(2) antibodies ranged from 10.8 ± 5.01 to 53.5 ± 1.92 nM as determined by Biacore analyses. The sequences of framework and complementarity-determining regions of ganglidiomab were identified. Finally, we demonstrated induction of a GD(2)-specific humoral immune response after vaccination of mice with ganglidiomab effective in mediating GD(2)-specific killing of neuroblastoma cells.
CONCLUSION
We generated and characterized a novel anti-idiotype antibody ganglidiomab and demonstrated activity against neuroblastoma.
Topics: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Base Sequence; Binding, Competitive; Cancer Vaccines; Cell Line, Tumor; Gangliosides; Humans; Kinetics; Mice; Molecular Sequence Data; Neuroblastoma; Protein Binding; Sequence Alignment
PubMed: 23591980
DOI: 10.1007/s00262-013-1413-y -
The AAPS Journal Jul 2017Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which...
Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Taking advantage of the immune system's ability to generate highly specific antibodies, the field has turned to anti-idiotype antibodies as powerful tools for the development of sensitive and specific bioassays. Here, we report the generation and characterization of a highly specific neutralizing anti-idiotype antibody directed against M9346A, the antibody moiety of mirvetuximab soravtansine. The anti-idiotype antibody recognizes M9346A with double-digit picomolar affinity, competes with folate receptor antigen for binding to M9346A, and can be used to develop both anti-drug-antibody and neutralizing antibody assays.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Humans; Immunoconjugates; Maytansine; Mice
PubMed: 28534292
DOI: 10.1208/s12248-017-0098-0 -
Journal of the National Cancer Institute Nov 1990Murine anti-idiotype monoclonal antibodies were generated against a human IgM monoclonal antibody (L612) that recognizes ganglioside GM3 on human melanoma. Hybridomas...
Murine anti-idiotype monoclonal antibodies were generated against a human IgM monoclonal antibody (L612) that recognizes ganglioside GM3 on human melanoma. Hybridomas secreting antibodies that bound specifically to L612 were selected by enzyme-linked immunosorbent assay using L612 and three negative control human IgMs, including monoclonal anti-GM2 and anti-GD2 antibodies, as well as purified serum IgM, as antigen sources. GM3-binding inhibition and cell-binding inhibition assays were used to identify seven anti-idiotype monoclonal antibodies that recognized determinants located within the antigen-combining sites of L612. To determine whether these anti-idiotype monoclonal antibodies possessed the internal image of the original antigen, we immunized syngeneic BALB/c mice with one of the anti-idiotype monoclonal antibodies, 4C10, coupled with keyhole limpet hemocyanin. Sera from the immunized mice reacted strongly with an antigen-positive M12 melanoma cell line and with purified GM3. Because L612 detects and kills melanoma tumor cells in vitro and in vivo in the presence of complement without affecting normal tissues, anti-idiotype monoclonal antibodies carrying the internal image of GM3 may be an effective tool for active specific immunotherapy in patients with melanoma.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antigens, Neoplasm; Culture Media; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M3) Ganglioside; Humans; Hybridomas; Immune Adherence Reaction; Immunization; Immunoglobulin G; Immunoglobulin M; Immunotherapy; Melanoma; Mice; Mice, Inbred Strains; T-Lymphocytes, Cytotoxic
PubMed: 1700134
DOI: 10.1093/jnci/82.22.1757 -
Nephron 1998Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This...
Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.
Topics: Animals; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Antigens; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Immunoglobulin A; Kidney; Mice; Mice, Inbred BALB C; Phosphorylcholine; Serum Albumin, Bovine
PubMed: 9578073
DOI: 10.1159/000044976