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Research on Vaccine for HIV/ AIDS NAcetilGM3 (GM3)

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The product

Monosialoganglioside N-acetyl GM3 (NAcGM3) is combined with Neisserial outer membrane vesicles to form very small proteoliposomes termed NAcGM3 / VSSP. NAcGM3 is non-covalently inserted in these nanometer-range vesicles and thereby rendered immunogenic, as shown in a number of animal species (Go to Publication).

Extensive preclinical data demonstrated NAcGM3 / VSSP anti-tumor protection in the B16 melanoma model. Both the ganglioside and the neisserial moieties of NAcGM3 / VSSP are essential to elicit anti-tumoral protection (Go to Publication), which is associated with the induction of a ganglioside-specific antibody response (Go to Publication)  and requires ganglioside expression on the tumor target (Go to Publication). Perioperative treatment with NAcGM3 / VSSP of melanoma-challenged mice abrogates the incidence of local recurrence and the development of lung metastasis, with survival of all tested animals (Go to Publication).

NAcGM3 immunogenicity in this particular formulation is most probably mediated by the powerful adjuvant properties of the neisserial components of the proteoliposomes. VSSP promotes, both in mice and humans, dendritic cell maturation (Go to Publication)  and cytokine secretion (Go to Publication)  in a Th1 promoting environment.

The clinical trials

Owing to its particular immunological properties (i.e. an immunogen for NAcGM3 and a Th1-promoting immune stimulator), NAcGM3 / VSSP clinical development has involved both cancer patients and HIV/AIDS patients. Several early-phase clinical trials with patients bearing NAcGM3-expressing tumors have been completed showing a satisfactory safety profile for NAcGM3 / VSSP (Go to Publication). The remarkably low toxicity prompted the investigation of NAcGM3 / VSSP immune modulating capacity in randomized clinical trials in HIV-infected individuals.

Two such studies are presently running at prestigious sites in Havana and Buenos Aires. Preliminary safety information confirms previous toxicity results even with concomitant administration of antiretroviral therapy. Reported adverse events include mild to moderate injection site reactions, fever, headache, chills and malaise. Immunological monitoring performed at the University of Buenos Aires showed a trend of slight expansion of NK cell- and CD8 effector cell-count, and decrease in T regulatory (Treg) cells in treated versus untreated patients. The current investigations are expected to indicate by 2009 – 2010 whether the course of infection and the efficacy of antiretroviral treatment is modified by NAcGM3 / VSSP administration. Favorable results would open up new lines of research for optimization of HIV/AIDS treatment.