The LADD Listeria monocytogenes cancer vaccine system

Listeria monocytogenes is a gram positive (no outer cell wall) bacteria which can cause a specific form of food poisoning called listeriosis. L. monocytogenes infection can occur without symptoms however if the symptoms of listeriosis develop there is a greater than 25% chance of death [1]. It is, however, an excellent vector for anti-cancer vaccines when appropriately engineered to eliminate virulence.

The principal benefits of Listeria as a cancer vaccine vector is that it is not neutralised by antibody binding as can occur with viral vectors and it infects antigen presenting cells including monocytes, macrophages and dendritic cells [2]. LADD (live-attenuated, double-deleted Listeria monocytogenes) is a vector system developed by Aduro Biotech [3]. LADD has two virulence genes deleted:  actA which facilitates the propulsion of the bacteria in the cytosol via actin polymerisation and inlB which mediates internalisation into non-antigen presenting cells such as endothelial cells [4].

The addition of cancer specific antigen genes to the LADD vector triggers immune responses against the cancer in immunised individuals. It is a very flexible system which could benefit greatly from the validation of additional cancer specific cell surface antigens. That said many clinical trials are underway that utilise LADD against multiple cancers including the hard to treat pancreatic cancer [5].

Refs

  1. ‘Listeria’. Accessed 9 February 2016. http://textbookofbacteriology.net/Listeria.html.
  2. Gravekamp, Claudia, and Yvonne Paterson. ‘Harnessing Listeria Monocytogenes to Target Tumors’. Cancer Biology & Therapy 9, no. 4 (15 February 2010): 257–65. doi:10.4161/cbt.9.4.11216.
  3. ‘LADD | Engineering Listeria Mononcytogenes Bacteria | Aduro BioTech’. Accessed 9 February 2016. http://www.aduro.com/pipeline/ladd/.
  4. Parida, Shreemanta K., Eugen Domann, Manfred Rohde, Simone Müller, Ayub Darji, Torsten Hain, Jürgen Wehland, and Trinad Chakraborty. ‘Internalin B Is Essential for Adhesion and Mediates the Invasion of Listeria Monocytogenes into Human Endothelial Cells’. Molecular Microbiology 28, no. 1 (1998): 81–93. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.1998.00776.x/full.
  5. ‘Clinical Trials | Aduro Biotech’. Accessed 9 February 2016. http://www.aduro.com/pipeline/clinical-trials/.
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