Outlining Novel Cellular Adjuvant Products for Therapeutic Vaccines Against Cancer

Josianne Nitcheu Tefit; Vincent Serra


Expert Rev Vaccines. 2011;10(8):1207-1220. 

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Alum Salts & Other Mineral Adjuvants

Alum is a component of several licensed human vaccines, including diphtheria–pertussis–tetanus, diphtheria–tetanus, diphtheria–tetanus combined with HBV, Haemophilus influenzae type B or inactivated polio virus, hepatitis A virus, Streptococcus pneumonia, meningococcal disease and human papilloma virus (HPV).[7] However, it is still not known exactly how alum mediates its adjuvant effects. Traditionally, Aluminum salts are thought to work through depot formation, releasing the antigen slowly into the body, thereby allowing antigen-specific lymphocytes to be exposed to the antigen for a longer time. More recent studies have demonstrated that aluminum activates the innate immune system through the Nod-like receptor, NLRP3 inflammasome, to produce inflammatory cytokines such as IL-1β and IL-18.[8] Alum is generally used to enhance antibody production,[9] and induces a mix of Th2 and Th1 cells in response to protein antigens in humans[10] and more profound polarized Th2-cell responses in mice. Unfortunately, alum salts are relatively weak adjuvants and rarely induce cellular immune responses[11–13] meaning that their utility for therapeutic cancer vaccines may be limited.

Nevertheless, a recent clinical trial combined alum with other adjuvants such as montanide adjuvant and recombinant (r)IL-12 in order to achieve maximum stimulation of the immune response. A total of 60 patients with high-risk resected melanoma were randomized to receive melanoma peptides gp100, MART-1 and tyrosinase with adjuvant Montanide™ ISA 51 and rIL-12. ELISPOT analyses of IFN-γ-secreting T cells over time in selected patients indicated that both an earlier increase in immunity and a slower decay back to baseline occurred in the higher dose IL-12/alum group than in the lower dose group, even when the peak responses were similar. Alum has emerged as playing an important role as demonstrated by a higher rate of postvaccine 6-month immune response to gp100 and MART-1 being observed in a group that received IL-12 plus alum, and by the immune response being associated with relapse-free survival. IL-12 may have directly augmented the activity of CD8+ T cells and/or may have polarized Th1 cells at the vaccine site to generate a more robust and long-lived cytolytic T-cell response, and alum may have played an important role owing to its sustained release effect.[14]


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