Improved Lipid A Based Adjuvant for Cancer Vaccines

Life Sciences : Therapeutics

Available for licensing

Inventors

  • Michael Trent, Ph.D. , Molecular Biosciences
  • Brittany Needham , University of Texas at Austin
  • David Giles , School of Biological Sciences
  • Marvin Whiteley, Ph.D. , Microbiology

Background/unmet need

Monophosphoryl lipid A, or MPL, is the first vaccine adjuvant to be approved by the FDA since the 1930s and is currently present in the widely used Human Papilloma Virus (HPV) vaccine Cervarix®. MPL provides many advantages over the prevailing adjuvant of aluminum salts—namely, the ability to stimulate the cellular immune response. Activation of the cellular immune response leads to destruction of cancerous or infected cells, making lipid A adjuvants particularly good candidates for cancer vaccines. Currently, MPL is produced by harvesting LPS from Salmonella minnesota, followed by several chemical processing and purification steps to achieve pure MPL.

Invention Description

The inventors have genetically engineered E. coli to synthesize the MPL lipid A structure on its surface. MPL can be harvested directly from this bacterium without risk of contamination with other potentially toxic lipid A species, eliminating the need for subsequent chemical processing. This method promises to be substantially cheaper and faster than current methods of producing MPL.

In addition to this MPL-producing strain, the inventors have genetically engineered E. coli strains expressing a wide range of lipid A profiles. Each lipid A variant elicits a unique profile of cytokine production and TLR4 responses, allowing the adjuvant to be tailored to achieve the desired immune response for a specific vaccine. In addition to the production of adjuvant, these strains can also be used for the production of safe whole cell vaccines.

Benefits/Advantages

  • Easy and cost effective production of MPL
  • Reduced risk of toxicity

Features

    64 E. coli strains producing unique lipid A species, including MPL

Market potential/applications

The global cancer vaccine market was worth $3.8 billion in 2010 and is expected to grow to $9 billion by 2018 (The Pharma Letter).
The global vaccine market is expected to approach $40 billion by 2015 (PharmPro.com)

Development Stage

Lab/bench prototype

IP Status