Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy.
OBJECTIVE
The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed.


METHODS
Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides.


RESULTS
The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested.


CONCLUSIONS
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.
Labrada
Mayrel
M
Center of Molecular Immunology, Vaccine Department, 216 St and 15th Ave., Atabey, Playa, P. O. Box 16040, Havana, 11600, Cuba. mayrel@cim.sld.cu
Clavell
Marilyn
M
Bebelagua
Yanín
Y
León
Joel de
Jd
Alonso
Daniel F
DF
Gabri
Mariano R
MR
Veloso
Roberto C
RC
Vérez
Vicente
V
Fernández
Luis E
LE
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism; D006736:Horses / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009345:Neisseria meningitidis / Q000276:immunology; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*
D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside