Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy

Labrada, Mayrel; Clavell, Marilyn; Bebelagua, Yanín; León, Joel de; Alonso, Daniel F.; Gabri, Mariano Rolando; Veloso, Roberto C.; Vérez, Vicente; Fernández, Luis E.

doi:10.1517/14712590903443084

Cited by 31 publications

(32 citation statements)

References 55 publications

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“…Interestingly, the anti-metastatic effect of the NGcGM3/VSSP vaccine was abolished in mice deficient in CD4 + T cells, suggesting the involvement of this population from the adaptive immune system in the anti-metastatic effect of the vaccine. In our first report 19 …”

Section: Discussionmentioning

confidence: 88%

“…Previously, a therapeutic benefit after sc NGcGM3/VSSP treatment of mice challenged with the 3LL-D122 tumor (spontaneous lung metastasis model) was documented. 19 So we wonder if, in the same experimental model, the intraperitoneal (ip) route of administration of the vaccine also produces an anti-metastatic effect. The NGcGM3/VSSP vaccine was injected ip or sc in different groups of mice, 7 and 14 d following the intra-footpad tumor cells implantation.…”

Section: Resultsmentioning

confidence: 99%

“…[24][25][26] We previously reported the immunogenicity of the NGcGM3/VSSP vaccine in chicken and mice models, and confirmed the capability of the sera of vaccinated animals to identify the ganglioside on positive NGcGM3 myeloma cells. 19 Furthermore, in the phase I clinical trial in advanced breast cancer patients, performed with NGcGM3/VSSP vaccine, all treated patients developed anti-NGcGM3 antibody titers (IgM and IgG) and the hyper-immune sera increased complementmediated cytotoxicity vs. NGcGM3 positive P3X63 myeloma cells. 16 In the controlled Phase II clinical trial conducted in patients with metastatic breast cancer with NGcGM3/VSSP, the vaccine was immunogenic and showed a sustained increase of both IgG and IgM antibody titters against NGcGM3.…”

Section: Discussionmentioning

confidence: 99%

“…19 Then we wondered if vaccination could increase the frequency of NK1.1 + cells in the lungs of these animals. Immunized or controls mice were sacrificed 3 d after the second vaccine administration and the frequency of NK and NKT cells measured by Flow Cytometry.…”

Section: Ngcgm3/vssp Directed Innate Immunity Effector Cells Toward Mmentioning

confidence: 99%

“…16,17 In a previous paper we showed that tumor cells express the NGcGM3 ganglioside in the murine model of spontaneous lung metastasis induced by the 3LL-D122 Lewis lung carcinoma tumor cells. 19 This murine model is much related to the disease occurring in cancer patients, who in many cases develop metastatic lesions after surgical treatment. The 3LL-D122 Lewis lung carcinoma spontaneous metastasis murine model was consistent While the NGcGM3/VssP vaccine, a preparation consisting in very small sized proteoliposomes (VssP) obtained by the incorporation of the NGcGM3 ganglioside into the outer membrane protein (OMP) complex of Neisseria meningitides, is currently studied in late stage clinical trials in breast cancer and melanoma patients, mechanisms involved in the vaccine's antitumor effect are insufficiently understood.…”

Section: Introductionmentioning

confidence: 99%

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Induction of leukocyte infiltration at metastatic site mediates the protective effect of NGcGM3-based vaccine

Labrada

Pablos²,

Prete³

et al. 2014

Human Vaccines & Immunotherapeutics

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ngcgm3/vssp Directed Innate Immunity Effector Cells Toward Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Induction of leukocyte infiltration at metastatic site mediates the protective effect of NGcGM3-based vaccine

Labrada

Pablos²,

Prete³

et al. 2014

Human Vaccines & Immunotherapeutics

Self Cite

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Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense

Boligan

Mesa

Fernández

et al. 2014

Cell. Mol. Life Sci.

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Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a 'microevolutionary' process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display 'enhanced self' to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein-glycan interactions. A better understanding of tumor 'glycan codes' as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

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Evaluation and evidence of natural gangliosides with two unsaturated bonds in the ceramide structure obtained by a combination of MALDI-MS and NMR spectroscopy

Arteaga¹,

Pita

López³

et al. 2011

Anal Bioanal Chem

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Gangliosides are membrane-associated glycosphingolipids. N-Acetyl GM3 and N-glycolyl GM3 are two tumor-associated antigens expressed in cancer tissues such as melanoma and mammalian cancer. In order to use these antigens in GM3-based vaccines for patients with early stage cancer, the synthetic version is recommended to avoid the risk of animal virus transmission from the source. However, the isolation of natural gangliosides is of comparative value for the structural characterization. The structures of N-acetyl and N-glycolyl GM3 extracted from dog and horse erythrocytes were evaluated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nuclear magnetic resonance techniques; additionally, the natural N-acetyl ganglioside was compared to a synthetic one. In addition to the main compound with C24:0 fatty acid chain, a minor component with an additional unsaturation in the ceramide chain was detected, in both the dog and the horse gangliosides. This paper shows spectroscopic evidence of the aforementioned compounds.

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Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy

Abstract: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.

Cited by 31 publications

References 55 publications

Induction of leukocyte infiltration at metastatic site mediates the protective effect of NGcGM3-based vaccine

Induction of leukocyte infiltration at metastatic site mediates the protective effect of NGcGM3-based vaccine

Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense

Evaluation and evidence of natural gangliosides with two unsaturated bonds in the ceramide structure obtained by a combination of MALDI-MS and NMR spectroscopy

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