Immunotherapy of Advanced Breast Cancer With a Heterophilic Ganglioside (NeuGcGM3) Cancer Vaccine

Carr, Adriana; Rodríguez, Edmundo; Arango, María del Carmen; Camacho, Rolando; Osorio, Marta; Gabri, Mariano Rolando; Carrillo, Guido; Valdés, Zolidina; Bebelagua, Yanín; Pérez, Rolando; Fernández, Luis E.

doi:10.1200/jco.2003.02.124

Cited by 90 publications

(79 citation statements)

References 23 publications

(9 reference statements)

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“…15 In the present study we demonstrated the NeuGcGM3 ganglioside expression in subcutaneous and lymph nodes metastasis of melanoma tumors. Gangliosides have been reported in plasma membrane essentially, 8 but some studies have shown the presence of gangliosides as GD3 in the cytoplasm of the mature neuronal cells.…”

Section: Discussionmentioning

confidence: 71%

“…In a previous clinical trial with this vaccine in advanced breast cancer patients, no vitiligo events were observed. 15 We did not find a direct association of vitiligo, the presence of anti-NeuGcGM3 ganglioside antibodies and the clinical outcome, but its relation with the vaccination process was evident, since it appeared after the administration of the first 5 vaccine doses and continued increasing after interrupting immunizations. In our case, it should be noticed that vitiligo was induced despite the fact that the vaccine formulation does not contain melanocyte antigens.…”

Section: Discussionmentioning

confidence: 90%

“…Antibody titers were lower than those obtained in breast cancer patients stage III, but very similar to those in breast cancer patients stage IV. 15 No relationship was observed between immunological response (serological and DTH) and the clinical outcome. The onset of DTH occurs on week 8, and at this time an increase of titers becomes evident.…”

Section: Discussionmentioning

confidence: 94%

“…Blood samples were analyzed as it was previously described. 15 Samples from 18 patients were also assessed for anti-NeuGcGM3 (NGcGM3) antibody titers with an ELISA test. Briefly, gangliosides (200 ng/well) in 50 μL of methanol were dried in 96-well polystyrene plates (Poly Sorp, Nunc, Denmark) for 90 minutes at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…14 Nevertheless, in spite of the tumor immunosuppression induced by this ganglioside, Carr et al, previously described the immunogenic and toxicity profile of the heterophilic NeuGcGM3 ganglioside vaccine in patients with advanced breast cancer. 15 This vaccine is formulated by the combination of the gangliosides with the outer membrane protein of Neisseria meningitides, to form very small size proteoliposomes (VSSP). 16 This technology allows for an active immunotherapy that involves activation of the potent innate natural immune system, a possible way to improve immunological and therapeutical results.…”

Section: Clinical Studymentioning

confidence: 99%

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Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

Osorio¹,

Gracia²,

Rodríguez³

et al. 2008

Cancer Biology & Therapy

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NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues.A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant.Twenty two patients were included, twelve at dose level of 200 μg and 10 at 400 μg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations.Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy.Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating antitumor immunity from autoimmunity deserve further research.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Clinical Studymentioning

confidence: 99%

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Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

Osorio¹,

Gracia²,

Rodríguez³

et al. 2008

Cancer Biology & Therapy

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Quantitative Screening of Cell‐Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection

et al. 2017

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As creening strategy involving designed extractors and collectors was used for the nondestructive quantitation of gangliosides on cell surfaces.T he extractors were constructed by functionalizing maleimide silica bubbles with aDNA probe, which contains an endonuclease cleavage site and ab oronic acid end to extract cell-surface sialic acid-containing compounds through simple centrifugation. After the extractors containing the extracted compounds were incubated with endonuclease,t he released oligonucleotide-gangliosides were selectively collected by silanized collector bubbles through hydrophobic interactions.The in vitro fluorescent signals from the collectors were used for the quantitation of cell-surface gangliosides.Bycombining with sialidase cleavage,aprotocol for the identification of ganglioside subtypes was developed. The successful monitoring of the regeneration of cell-surface gangliosides demonstrates the potential of this strategy in probing related biological processes.

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Quantitative Screening of Cell‐Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection

et al. 2017

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A screening strategy involving designed extractors and collectors was used for the nondestructive quantitation of gangliosides on cell surfaces. The extractors were constructed by functionalizing maleimide silica bubbles with a DNA probe, which contains an endonuclease cleavage site and a boronic acid end to extract cell-surface sialic acid-containing compounds through simple centrifugation. After the extractors containing the extracted compounds were incubated with endonuclease, the released oligonucleotide-gangliosides were selectively collected by silanized collector bubbles through hydrophobic interactions. The in vitro fluorescent signals from the collectors were used for the quantitation of cell-surface gangliosides. By combining with sialidase cleavage, a protocol for the identification of ganglioside subtypes was developed. The successful monitoring of the regeneration of cell-surface gangliosides demonstrates the potential of this strategy in probing related biological processes.

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Immunotherapy of Advanced Breast Cancer With a Heterophilic Ganglioside (NeuGcGM3) Cancer Vaccine

Abstract: NeuGcGM3/VSSP/Montanide ISA 51 is an unusual immunogenic ganglioside vaccine and also seems to be safe in this small trial. Immunologic surrogates of activity indicate that this reagent warrants further investigation.

Cited by 90 publications

References 23 publications

Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

Quantitative Screening of Cell‐Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection

Quantitative Screening of Cell‐Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection

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