Engineering flaw may render cancer vaccines ineffective

Cancer vaccine freund's adjuvant

Some cancer vaccines may be ineffective because of an engineering flaw in the vaccine's design, a study has found.

Research performed at Texas MD Anderson Cancer Center and published in Nature Medicine examined the T cell responses elicited in mice after vaccination with the cancer vaccine gp100 melanoma peptide. The aim of the cancer immunotherapy is to increase the levels of T cells in the blood and direct them towards the tumour cells. However, after following fluorescently tagged T cells to see where they went, researchers found that the T cells accumulated around the vaccine injection site rather than in the tumour.

The cause?

Possibly a mineral oil-based adjuvant, incomplete Freund's adjuvant (IFA), commonly added to vaccines with the aim of boosting the immune response.

When IFA was included in the vaccine formulation, the fluorescently tagged CD8+ T cells sequestered around the antigen-rich vaccination site where they became dysfunctional and underwent interferon-γ (IFN-γ)- and Fas ligand (FasL)-mediated apoptosis. When IFA was removed from the formula and replaced with a saline solution and covax (a combination of three stimulatory molecules), however, the T cells instead travelled to the tumour cells to destroy them.

IFA offers a very attractive target for T cells – more attractive than the tumour itself – and since IFA can persist at the vaccination site for several months, the T cells will persist at the site and damage local tissues.

The use of IFA in the vaccine formulation may therefore be the cause of lesions at the vaccine injection site and the failure of the T cells to target the tumour. A formulation that does not include IFA may result in greater therapeutic efficacy of peptide-based cancer vaccines.

You might be interested in reading about the promising results that novel cancer immunotherapy Flagrp-170 has recently shown in trials.

Why not join in our discussion about cancer vaccines on our LinkedIn discussion page.

If you want to hear more about the cancer vaccine landscape overview, including a talk on harnessing the power of the immune system to build strong cancer vaccines, you might be interested in attending the World Vaccine Congress & Expo 2013, 16-18 April 2013, at the Gaylord National Hotel and Convention Center, Washington DC. You can download the brochure here.

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