Generation of anti-Neu-glycolyl-ganglioside antibodies by immunization with an anti-idiotype monoclonal antibody: A self versus non-self-matter

Hernández, Ana; Rodríguez, Mabel; López‐Requena, Alejandro; Beausoleil, Irene; Pérez, Rolando; Vázquez, Ana María

doi:10.1016/j.imbio.2005.02.002

Cited by 34 publications

(21 citation statements)

References 36 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An important finding of this study was the detection of a high level of non-suppressible immune reactivity to NeuGcGM3 ganglioside by the adsorption of patient sera with 1E10 mAb. A similar finding in preclinical studies was reported by Lange and Lemke in mice immunized with an Ab against phenyl-oxazolone (47), and by ourselves in chickens immunized with 1E10 mAb (32). The presence of these Id Ϫ Ag ϩ Abs due to the immunization of NSCLC patients with 1E10 mAb also confirm the results obtained in advanced melanoma and breast cancer patients treated with this anti-Id mAb (20,26).…”

Section: Discussionsupporting

confidence: 88%

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Hernández¹,

Toledo²,

Martínez³

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

1E10 mAb is an anti-Id murine mAb (Ab2 mAb) specific for an Ab1 mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In preclinical studies, this Ab2 Ab was able to mimic NeuGc-containing gangliosides only in animals lacking expression of these Ags in normal tissues. In this study, we report on the immune responses elicited in 20 non-small cell lung cancer patients treated with 1 mg of aluminum hydroxide-precipitated 1E10 mAb. In the hyperimmune sera from 16 of 20 patients, a strong specific Ab response of both IgM and IgG isotypes against NeuGcGM3 ganglioside was observed. Patient immune sera were able to induce complement-independent cell death of NeuGcGM3-expressing X63 murine myeloma target cells. Significant immunoreactivity to NeuGcGM3 was still detected after the complete abrogation of the reactivity against 1E10 mAb by the adsorption of patient sera with this Ab. We hypothesize that Id−Ag+ Abs could reflect the activation of an autologous idiotypic cascade into the patients. Both Id+Ag+ and Id−Ag+ fractions were separated by affinity chromatography and characterized. Although IgG isotype Abs were found in both fractions, IgM isotype Abs were found only in the Id−Ag+ fraction. Both Id+Ag+ and Id−Ag+ Abs were able to specifically recognize and induce cell death in NeuGcGM3-expressing X63 myeloma target cells. Patients that developed IgG and/or IgM Abs against NeuGcGM3 showed longer median survival times.

show abstract

Section: Discussionsupporting

confidence: 88%

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Hernández¹,

Toledo²,

Martínez³

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…To overcome this limitation, one approach has been to use as an immunogen a paratope-specific anti-idiotypic NAb that mimics tumor-specific carbohydrate residues, such as sialyl-glycolyl gangliosides, which are expressed on several types of tumors [28]. Murine anti-idiotypic antibodies were generated against a murine mAb P3, which specifically binds sialyl-glycolyl gangliosides.…”

Section: Reviewmentioning

confidence: 99%

“…One of these anti-idiotypic Abs (1E10) has germline configuration and belongs to the V(H)J558 and Vk10 gene family. Subsequently, nonsmall-cell lung cancer patients were hyperimmunized with this anti-idiotypic Ab and successfully induced Abs that recognize the same gangliosides as the P3 mAb [28,29]. In fact, those patients who elicited anti-sialyl-glycolyl antibodies showed a longer survival.…”

Section: Reviewmentioning

confidence: 99%

Naturally occurring auto-antibodies in homeostasis and disease

Lutz

Binder

Kaveri

2009

Trends in Immunology

166

View full text Add to dashboard Cite

“…P3 is a monoclonal antibody, generated in BALB/c mice [1], that has the unique ability to induce in a syngeneic model a strong anti-idiotypic response in the absence of adjuvant or carrier protein [5, 14], which is not a frequently observed phenomenon [6, 48–50]. P3 was originally selected due to its binding to N -glycolylated gangliosides, but it also recognizes other self-molecules like sulfatides [1].…”

Section: Discussionmentioning

confidence: 99%

B-CD8⁺T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

Martínez

Pupo

Cabrera

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo. Interestingly, transfer of both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion of IFN-γ and IL-4, although this activation was not detected ex vivo. Interestingly, naïve CD8+ T cells increased the expression of activation markers and IFN-γ secretion in the presence of B-1a cells isolated from P3 mAb-immunized mice, even without in vitro restimulation. In contrast, B-2 cells were able to stimulate CD8+ T cells only if P3 was added in vitro. Using bioinformatics, a MHC class I-binding peptide from P3 VH region was identified. P3 mAb was able to induce a specific CTL response in vivo against cells presenting this peptide. Both humoral and CTL anti-idiotypic responses could be mechanisms to protect against the self-reactive antibody, contributing to keeping the tolerance to self-antigens.

show abstract

Generation of anti-Neu-glycolyl-ganglioside antibodies by immunization with an anti-idiotype monoclonal antibody: A self versus non-self-matter

Cited by 34 publications

References 36 publications

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Naturally occurring auto-antibodies in homeostasis and disease

B-CD8⁺T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

Contact Info

Product

Resources

About

Generation of anti-Neu-glycolyl-ganglioside antibodies by immunization with an anti-idiotype monoclonal antibody: A self versus non-self-matter

Cited by 34 publications

References 36 publications

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

Naturally occurring auto-antibodies in homeostasis and disease

B-CD8+T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

Contact Info

Product

Resources

About

B-CD8⁺T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody