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

Labrada, Mayrel; Pablos, Isabel; Prete, Francesca; Hevia, Giselle; Clavell, Marilyn; Benvenuti, Federica; Fernández, Luis E.

doi:10.4161/hv.29161

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…Previously, Labrada et al showed the increased expression of NeuGcGM3 from primary tumors to metastatic lesions in 3LL-D122 tumor model [ 24 ]. Anti-metastatic effect of NeuGcGM3/VSSP vaccine which targeting this ganglioside was observed in this lung model, previously [ 24 , 25 ]. Here, we described for the first time, a positive staining of NeuGcGM3 expression in lung metastasis induced by 4T1-cells, as second model.…”

Section: Discussionsupporting

confidence: 74%

Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it’s potential therapeutic implications

Palomo

Blanco

Pérez³

et al. 2016

Clin Exp Metastasis

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Interaction between epidermal growth factor receptor (EGFR) signaling with GM3 ganglioside expression has been previously described. However, little is known about EGFR and NeuGcGM3 co-expression in cancer patients and their therapeutic implications. In this paper, we evaluate the co-expression of EGFR and NeuGcGM3 ganglioside in tumors from 92 patients and in two spontaneous lung metastasis models of mice (Lewis lung carcinoma (3LL-D122) in C57BL/6 and mammary carcinoma (4T1) in BALB/c). As results, co-expression of EGFR and NeuGcGM3 ganglioside was frequently observed in 63 of 92 patients (68 %), independently of histological subtype. Moreover, EGFR is co-expressed with NeuGcGM3 ganglioside in the metastasis of 3LL-D122 and 4T1 murine models. Such dual expression appears to be therapeutically relevant, since combined therapy with mAbs against these two molecules synergistically increase the survival of mice treated. Overall, our results suggest that NeuGcGM3 and EGFR may coordinately contribute to the tumor cell biology and that therapeutic combinations against these two targets might be a valid strategy to explore.

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Section: Discussionsupporting

confidence: 74%

Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it’s potential therapeutic implications

Palomo

Blanco

Pérez³

et al. 2016

Clin Exp Metastasis

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“…The anti-tumor activity of 7A7 mAb [ 35 ] and NGcGM3/VSSP vaccine [ 29 , 36 ] depends of the induction of the cellular immune effectors, in the 3LL-D122-models. Then, we explore the contribution of CD4 + T, CD8 + T and NK1.1 + cells on the synergistic effect of the combination therapy in the 3LL-D122 model.…”

Section: Resultsmentioning

confidence: 99%

Synergistic potentiation of the anti-metastatic effect of anti EGFR mAb by its combination with immunotherapies targeting the ganglioside NGcGM3

et al. 2018

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Several Anti-EGFR mAbs are register for the treatment of human cancer. However, their impact on patients overall survival has been limited by tumor resistance. N-Glycolyl variant of GM3 ganglioside (NGcGM3) is specifically expressed in some human tumors, and it has been associated with a poor prognosis. Several reports have documented that GM3 physically associates to EGFR inhibiting its ligand depend phosphorylation, but it also facilitates an alternative/compensatory signaling cascade mediated by Uroquinase Plasminogen Activator Receptor (uPAR) and integrin α5β1 interaction. However, the difference between NGc and N-Acetylated (NAc) variants of GM3 regarding such interactions is unknown. We hypothesized that enrichment of NGcGM3 expression in tumors relates to advantages of this ganglioside, on ensuring both EGFR and uPAR pathways optimal function. We explored the impact of combining an anti-EGFR (7A7 mAb) with anti-NGcGM3 therapies: NGcGM3/VSSP vaccine or 14F7 mAb. Both combinations synergistically increase overall survival in two models of lung metastasis: 3LL-D122 and 4T1; but combination with NGcGM3/VSSP vaccine is significantly more effective. In 3LL-D122-metastasis, of mice treated with the best combination, both EGFR and uPAR/α5β1 integrin pathways are turn off (I.e expression of uPAR/α5β1; and phosphorylation of EGFR, Stat3, Src and FAK are reduced); and tumor angiogenesis is decreased. Interestingly, combination treatment increases tumor infiltrating CD4+T, CD8+T and NK+-cells. Furthermore, a positive clinical outcome is reported for a cancer patient treated with an anti-EGFR mAb and anti-NGcGM3 therapy. Overall, our results support the combination of anti EGFR antibodies with therapies targeting NGcGM3 to increase their efficacy in future clinical trials.

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GM3(Neu5Gc) ganglioside: an evolution fixed neoantigen for cancer immunotherapy

Labrada

Dorvignit

Hevia

et al. 2018

Seminars in Oncology

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

Cited by 3 publications

References 44 publications

Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it’s potential therapeutic implications

Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it’s potential therapeutic implications

Synergistic potentiation of the anti-metastatic effect of anti EGFR mAb by its combination with immunotherapies targeting the ganglioside NGcGM3

GM3(Neu5Gc) ganglioside: an evolution fixed neoantigen for cancer immunotherapy

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