Generation of Human Monoclonal Antibodies Against Ganglioside Antigens and Their Applications in the Diagnosis and Therapy of Cancer

Alfonso, Mauro; Zeuthen, Jesper

doi:10.3109/02841869609101643

Cited by 8 publications

(3 citation statements)

References 42 publications

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“…In attempts to enhance their immunogenicity in mice, many studies have converted gangliosides to TD antigens by conjugation to proteins or incorporation into protein-enriched liposomes (1,26,31,38). Indeed, we show here that BALB/c mice immunized with GQ1b-ova liposomes do generate lowlevel anti-GQ1b responses that show characteristics of a memory response.…”

Section: Vol 70 2002 Tolerance To Gangliosides and Campylobacter Inmentioning

confidence: 65%

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

et al. 2002

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Guillain-Barré syndrome followingCampylobacter jejuni infection is frequently associated with anti-ganglioside autoantibodies mediated by molecular mimicry with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The regulation of antibody responses to these T-cell-independent antigens is poorly understood, and only a minority of Campylobacter-infected individuals develop anti-ganglioside antibodies. This study investigates the response to gangliosides and LPS in strains of mice by using a range of immunization strategies. In normal mice following intraperitoneal immunization, antibody responses to gangliosides and LPS are low level but can be enhanced by the antigen format or coadministration of protein to recruit T-cell help. Class switching from the predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels, suggesting B1-cell involvement. Systemic immunization results in poor responses. In GalNAc transferase knockout mice that lack all complex gangliosides and instead express high levels of GM3 and GD3, generation of anti-ganglioside antibodies upon immunization with either complex gangliosides or gangliosidemimicking LPS is greatly enhanced and exhibits class switching to T-cell-dependent IgG isotypes and immunological memory, indicating that tolerance to self gangliosides is a major regulatory factor. Responses to GD3 are suppressed in knockout mice compared with wild-type mice, in which responses to GD3 are induced specifically by GD3 and as a result of polyclonal B-cell activation by LPS. The anti-ganglioside response generated in response to LPS is also dependent on the epitope density of the ganglioside mimicked and can be further manipulated by providing secondary signals via lipid A and CD40 ligation.

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Section: Vol 70 2002 Tolerance To Gangliosides and Campylobacter Inmentioning

confidence: 65%

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

et al. 2002

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“…These tumor cells associated GSL guided mAbs have been used in cytological and pathology exams trying to differentiate benign lesions from malignant tumors 17 . Despite promising results, so far, the use of GSLs in cancer diagnosis and treatment is still restrict to some types of tumors, such as melanomas 9,30,31 .…”

Section: Discussionmentioning

confidence: 99%

Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior

Filho

Walder

Takahashi

et al. 2006

Rev. Bras. Otorrinolaringol.

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Os glicoesfingolipídios (GSLs) são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC) é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57µg/mg) em comparação à mucosa normal (1,92µg/mg), principalmente do monosialogangliosídeo (GM3), trihexosilceramida (CTH), dihexosilceramida (CDH), globosídeo (Gb4). A expressão de monohexosilceramida (CMH) foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3). Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.

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“…It has also been shown that the expression of specific gangliosides is reflected in the malignancy grade of the tumour [3,14,47,52,58]. Furthermore, human monoclonal antibodies (MAbs) to several ganglioside antigens, such as GM2, GD2, GD3 and GM3, have been explored in melanoma therapy [1].…”

Section: Introductionmentioning

confidence: 99%

The glioma‐associated gangliosides 3′‐isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains

Hedberg

Mahesparan

Read

et al. 2001

Neuropathology Appl Neurobio

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This work describes the in vivo expression and distribution of glioma-associated gangliosides (GD3, GM2, 3'-isoLM1) in a novel human brain tumour nude rat xenograft model. In this model, the tumours, which are established directly from human glioblastoma biopsies, show extensive infiltrative growth within the rat brain. This model therefore provides an opportunity to study ganglioside expression not only within the macroscopic tumour, but also in brain areas with tumour cell infiltration. The ganglioside expression was studied by confocal microscopy of immunostained brain sections using antiganglioside monoclonal antibodies. Xenografts from four human glioblastoma multiformes were established in rats and the brains removed after 3-4 months. Ganglioside GD3 was expressed in the tumour parenchyma while ganglioside 3'-isoLM1 was more abundantly expressed in the periphery of the tumour associated with areas of tumour cell invasion. GM2 expression was only seen in one tumour, where it was located within the main tumour mass. Double staining with a pan antihuman monoclonal antibody (3B4) and the antiganglioside monoclonal antibodies confirmed that the ganglioside expression was associated with tumour cells. This work supports the concept of different biological roles for individual gangliosides and indicates that antibodies or ligands directed against GD3 and 3'-isoLM1 might be complementary when applied in the treatment of human glioblastomas.

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Generation of Human Monoclonal Antibodies Against Ganglioside Antigens and Their Applications in the Diagnosis and Therapy of Cancer

Cited by 8 publications

References 42 publications

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior

The glioma‐associated gangliosides 3′‐isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains

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