Science News
from research organizations

Using a molecular switch to turn on cancer vaccines

Date:
March 7, 2011
Source:
Journal of Clinical Investigation
Summary:
Researchers have attempted to capitalize upon natural immune responses against tumors to develop new therapies by generating dendritic cells (DCs) to use as vaccines to augment the T-cell responses of cancer patients. In a new study, researchers improved DC maturation protocols for vaccine production. They engineered a form of the adaptor protein MyD88 that induced downstream signaling in response to a drug. The researchers hope that this "switch" might be broadly applicable to the design of DC vaccines.
Share:
       
FULL STORY

The immune system is capable of recognizing tumor growth, and naturally mounts an anti-cancer defense. Dendritic cells (DCs) can take up tumor-derived molecules (antigens) and present them to T cells, and those "primed" T cells are then able to recognize and kill tumor cells.

In recent years, researchers have attempted to capitalize upon these natural immune responses to develop new therapies- namely, by generating a pool of tumor antigen-pulsed DCs that might be used as vaccines to augment the T-cell responses of cancer patients. In clinical trials, these DC vaccines have had limited success, in part because the protocols to generate mature and active DCs in vitro are imperfect. Specifically, generation of mature DCs requires activation of Toll-Like receptors (TLRs), usually achieved by administration of lipopolysaccharide, which can cause toxic shock in humans and can promote apoptosis.

In a new paper, David Spencer and colleagues, of Baylor University in Houston, Texas, addressed this problem by looking to the adaptor molecule downstream of the TLR, MyD88. They engineered a form of MyD88 that could induce downstream signaling in response to a drug, and expressed this inducible MyD88 (iMyD88) in DCs.

Further, the researchers combined iMyD88 with a second pathway required for optimal activation of DCs- CD40 signaling- so that they could control both pathways with administration of a single drug. This combination improved DC-mediated tumor antigen-specific T cell responses in mouse cancer models and T cell responses to human tumor antigens. The researchers hope that this "switch" might be broadly applicable to the design of DC vaccines.

The research appears in the Journal of Clinical Investigation.


Story Source:

The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Priyadharshini Narayanan, Natalia Lapteva, Mamatha Seethammagari, Jonathan M. Levitt, Kevin M. Slawin, David M. Spencer. A composite MyD88/CD40 'switch' synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI44327

Cite This Page:

Journal of Clinical Investigation. "Using a molecular switch to turn on cancer vaccines." ScienceDaily. ScienceDaily, 7 March 2011. <www.sciencedaily.com/releases/2011/03/110307124520.htm>.
Journal of Clinical Investigation. (2011, March 7). Using a molecular switch to turn on cancer vaccines. ScienceDaily. Retrieved September 2, 2015 from www.sciencedaily.com/releases/2011/03/110307124520.htm
Journal of Clinical Investigation. "Using a molecular switch to turn on cancer vaccines." ScienceDaily. www.sciencedaily.com/releases/2011/03/110307124520.htm (accessed September 2, 2015).

Share This Page: