Chapter Details

Pub Date: 5 Nov 2009
Pages: 13
Chapter Category: Oncology
Taken from the Book: Lipid A in Cancer Therapy
Book Series: Special Books
Edited by: Jean-François Jeannin

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Monophosphoryl Lipid A (MPL) as an Adjuvant for Anti‑Cancer Vaccines:\r\nClinical Results

Christopher W. Cluff

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A variety of vaccines designed for cancer immunotherapy have been tested in clinical trials for more than two decades. Investigators realized early on that addition of adjuvants to cancer vaccines would be required to overcome the poor immune responses that are generally elicited to antigens contained within these vaccines. Although the effectiveness of LPS as an immunomodulator has long been known, the pharmacologic use of purified LPS (or lipid A) as an adjuvant is precluded by its toxicity. In this regard, LPS is highly pyrogenic and promotes systemic inflammatory response syndrome.72 In an effort to uncouple the immunomodulatory effects of lipid A from its toxicity, Ribi et al developed 3‑O‑desacyl‑4’‑monophosphoryl lipid A (MPL), which comprises the lipid A portion of LPS from which the (R)‑3‑hydroxytetradecanoyl group and the 1‑phosphate have been removed9 by successive acid and base hydrolysis. LPS and MPL induce similar cytokine profiles, but MPL is at least 100‑fold less toxic.9,10 MPL, as the active ingredient in MPL™ adjuvant or as one of the active ingredients in Detox™™ adjuvant (with CWS and oil), AS02B adjuvant (with QS21 in an oil in water emulsion) or AS15 ( a liposomal formulation with QS21 and CpG), has been administered to more than 300,000 human subjects in studies of next‑generation vaccines,11 including the patients enrolled in the clinical trials discussed in this review. At this time, MPL is the only lipid A derivative that has been clinically tested as an adjuvant for cancer vaccines.\r\n

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