Antibody Response to Immunization with Purified GD3 Ganglioside and GD3 Derivatives (Lactones, Amide and Gangliosidol) in the Mouse

Ritter, Gerd; Boosfeld, Erika; Calves, Michele; Oettgen, Herbert F.; Old, Lloyd J.; Livingston, Philip O.

doi:10.1016/s0171-2985(11)80581-4

Cited by 35 publications

(9 citation statements)

References 28 publications

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“…These results suggest that ManNPr, ManNBu, ManNiBu, ManNPiv and ManNPhAc may be used as effective biosynthetic precursors to engineer cell surface sialic acid. Coupled with the fact that artificially modified sialooligosaccharides are highly immunogenic, [33][34][35] these results should be valuable for the development of new cancer immunotherapies. Among the potentially useful biosynthetic precursors identified, ManNiBu and ManNPhAc are especially interesting to us, because our initial studies also indicated that N-iBu and N-PhAc modified sialic acids could induce robust IgG antibodies desirable for cancer immunotherapy.…”

Section: Resultsmentioning

confidence: 99%

Accessibility of N-acyl-d-mannosamines to N-acetyl-d-neuraminic acid aldolase

Pan

Ayani

Nadas

et al. 2004

Carbohydrate Research

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N-Acetyl-D-neuraminic acid (NeuNAc) aldolase is an important enzyme for the metabolic engineering of cell surface NeuNAc using chemically modified D-mannosamines. To explore the optimal substrates for this application, eight N-acyl derivatives of D-mannosamine were prepared, and their accessibility to NeuNAc aldolase was investigated quantitatively. The N-propionyl-, Nbutanoyl-, N-iso-butanoyl-, N-pivaloyl-and N-phenylacetyl-D-mannosamines proved to be as good substrates as, or even better than, the natural N-acetyl-D-mannosamine, while the Ntrifluoropropionyl and benzoyl derivatives were poor. It was proposed that the electronic effects might have a significant influence on the enzymatic aldol condensation reaction of D-mannosamine derivatives, with electron-deficient acyl groups having a negative impact. The results suggest that N-propionyl-, N-butanoyl-, N-iso-butanoyl-and N-phenylacetyl-D-mannosamines may be employed to bioengineer NeuNAc on cells.

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Section: Resultsmentioning

confidence: 99%

Accessibility of N-acyl-d-mannosamines to N-acetyl-d-neuraminic acid aldolase

Pan

Ayani

Nadas

et al. 2004

Carbohydrate Research

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“…Several reports indicated that chemical modification of gangliosides could augment their immunogenicity. We prepared a series of synthetic ganglioside congeners and adhered them to BCG to induce antibody in laboratory animals and melanoma patients (Ritter et al, 1990a(Ritter et al, ,b, 1991. GD3 amide, GD3 gangliosidol, GD3-L I and II and GD3 acetylated at various sites were all more immunogenic than GD3, but the increased antibody titers induced by these synthetic congeners of GD3 were not reactive with unmodified GD3 or melanoma cells (Ritter et al, 1990a,b).…”

Section: Discussionmentioning

confidence: 99%

“…Murine MAbs reactive with other ganglioside lactones are also reactive with the parent ganglioside (Bosslet et al, 1989;Dohi et al, 1988;Tai et al, 1988). Serum antibodies induced by immunization of mice with GD3-LI (the lactone ring formed between the carboxyl group of sialic acid and the hydroxyl group of the ganglioside) were shown to react with purified GD3 and GD3 expressing human melanoma cells (Ritter et al, 1990a). With GD3-L/BCG, we were able to induce low-titer antibodies against GD3-L in 4 of 9 patients.…”

Section: Discussionmentioning

confidence: 99%

Induction of antibodies against GD3 ganglioside in melanoma patients by vaccination with GD3-lactone-KLH conjugate plus immunological adjuvant QS-21

et al. 2000

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“…14–19 For both GD2L and GD3L, the lowest optimal dose was 30 mcg per vaccine. 18,19 For QS-21, doses of 50–200 mcg were tested and found safe, with side effects of grade 3 erythema and flu-like symptoms lasting 2–4 days.…”

Section: Introductionmentioning

confidence: 99%

Phase I Trial of a Bivalent Gangliosides Vaccine in Combination with β-Glucan for High-Risk Neuroblastoma in Second or Later Remission

Kushner

Cheung

Modak

et al. 2014

Clinical Cancer Research

123

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Background To report on a phase I trial designed to find the maximally tolerated dose in children of the immunological adjuvant OPT-821 in a vaccine containing neuroblastoma-associated antigens (GD2 and GD3) (Clinicaltrials.gov NCT00911560). Secondary objectives were to obtain preliminary data on immune response and activity against minimal residual disease (MRD). Treatment also included the immunostimulant β-glucan. Methods Neuroblastoma patients in ≥2nd complete/very good partial remission received vaccine subcutaneously (weeks 1-2-3-8-20-32-52). Vaccine contained 30 µg each of GD2 and GD3 stabilized as lactones and conjugated to the immunological carrier protein keyhole limpet hemocyanin; and OPT-821 which was dose-escalated as 50, 75, 100 and 150 µg/m2 per injection. Oral β-glucan (40 mg/kg/day, 14 days on/14 days off) started week 6. Results The study was completed with 15 patients because there was no dose-limiting toxicity at 150 µg/m2 of OPT-821 (the dosing used in adults). 13/15 patients received the entire protocol treatment including 12 who remain relapse-free at 24+ to 39+ (median 32+) months and one who relapsed (single node) at 21 months. Relapse-free survival was 80±10% at 24 months. Vaccine and β-glucan were well tolerated. 12/15 patients had antibody responses against GD2 and/or GD3. Disappearance of MRD was documented in 6/10 patients assessable for response. Conclusions This immunotherapy program lacks major toxicity and is transportable to any outpatient clinic. Patient outcome is encouraging but the efficacy is uncertain because of the complexity and heterogeneity of prior therapies. A larger phase II trial is underway.

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Antibody Response to Immunization with Purified GD3 Ganglioside and GD3 Derivatives (Lactones, Amide and Gangliosidol) in the Mouse

Cited by 35 publications

References 28 publications

Accessibility of N-acyl-d-mannosamines to N-acetyl-d-neuraminic acid aldolase

Accessibility of N-acyl-d-mannosamines to N-acetyl-d-neuraminic acid aldolase

Induction of antibodies against GD3 ganglioside in melanoma patients by vaccination with GD3-lactone-KLH conjugate plus immunological adjuvant QS-21

Phase I Trial of a Bivalent Gangliosides Vaccine in Combination with β-Glucan for High-Risk Neuroblastoma in Second or Later Remission

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