Enhancing Immunogenicity of Cancer Vaccines: QS-21 as an Immune Adjuvant

Saponins comprise a class of plant natural products that incorporate a lipophilic terpenoid core, to which is appended one or more carbohydrate residues. They are amphiphilic molecules and often exhibit toxic biological profiles, likely as a result of their roles as vital components in protective coatings to defend against phytopathogen infection and insect predation. The most notable of adjuvant-active saponins investigated for vaccine development come from the Chilean Soapbark Tree, Quillaja saponaria (i.e., QS). More than 30 years ago, semi-purified extracts (i.e., Quil A) from the cortex of Quillaja saponaria were found to be highly effective as adjuvants in veterinary vaccines. However, due to significant and variable toxicity effects, Quil A was not deemed appropriate for human vaccines. More refined purification methods have led to multiple fractions which are derived from the original plant extract. As such, QS-21 to date appears to be one of the more scientifically interesting and robust adjuvants in use in vaccinology. The role of QS-21 as an adjuvant for use in a variety of cancer vaccine trials and its comparison to other adjuvants is discussed in this review.