Outlining Novel Cellular Adjuvant Products for Therapeutic Vaccines Against Cancer

Josianne Nitcheu Tefit; Vincent Serra


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

In This Article

Tensoactive Agents

Saponins (Quil-A, ISCOM, QS-2) are tensoactive triterpene glycosides isolated from plants[94,95] and containing a hydrophobic nucleus of triterpenoid structure with carbohydrate chains linked to the nucleus.[96] Saponins induce a strong adjuvant effect to T-dependent as well as T-independent antigens. Saponins also induce strong cytotoxic T lymphocyte (CTL) responses and potentiate the response to mucosal antigens.[96]


Quil-A and its derivatives, extracted from the bark of the Quillaja saponaria tree, is composed of a heterogeneous mixture of triterpene glycosides. Fractions purified from this extract by reverse phase chromatography, mainly QS-21, have been studied as alternatives to alum when strong cellular responses are required for a particular vaccine.[96–98] Quil-A is generally considered too toxic for human use and has been widely used as an adjuvant in veterinary vaccines.[99]


Antigenics' (Lexington, MA, USA) QS-21 Stimulon adjuvant is one of the most widely tested vaccine adjuvants under development. QS-21 is a purified component of Quil-A that demonstrates low toxicity and maximum adjuvant activity. There is rationale for including this component in cancer vaccine formulations as QS-21 has been shown to stimulate antibody as well as CD4+ Th1 and CTL responses to subunit antigens. Several clinical trials using QS-21 have been performed by Livingston and colleagues, who have reported good immunogenicity in patients with several tumor types.[100,101]

QS-21 is currently being evaluated as an adjuvant for many different vaccine candidates, both by itself as well as in combination with other immunostimulatory components. QS-21 is in clinical trials, of which several are in late-stage development by Antigenics' licensees, including GSK. GSK uses QS-21 as a key component in several of their proprietary adjuvant systems, which play an integral role in a new generation of GSK vaccines currently in development (discussed in further detail in later sections of this article).

Immunostimulating Complex ISCOMATRIX®

Partially purified fractions of Quil-A have also been used in ISCOM composed of antigen, phospholipids, cholesterol and Quil-A fractions. ISCOMs are approximately 40-nm cage-like particles trapping the protein antigen through hydrophobic interactions, while ISCOMATRIX® (CSL Ltd, Australia; preformed antigen-free particles) provides for more general applications by accommodating nonhydrophobic antigens. Recombinant NY-ESO-1 protein administered ISCOMATRIX adjuvant has been found to be highly immunogenic in patients with resected melanoma.[102,103] A Phase II study of NY-ESO-1 ISCOMATRIX vaccine in patients with resected stage IIc, III or IV malignant melanoma examined the clinical and immunologic efficacy of the vaccine in patients with advanced metastatic melanoma and showed that NY-ESO-1-specific cellular immune responses were attenuated in patients with advanced melanoma compared with those seen in the previous trial in patients with fully resected disease. In particular, peptide-specific CD4+ and CD8+ T-cell responses in blood and in skin as delayed-type hypersensitivity reactions were significantly impaired. In these patients, regulatory lymphocytes were increased in the blood, reflecting a potentially more immunosuppressive environment in vivo.[104] Enhancement of immunity by reducing tumor-induced immune suppression may allow better immunization of patients with advanced melanoma and consequently improve the prospect of clinical responses.


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