Gene Therapy Enhances Survival of Cancer-Killing Dendritic Cells

Researchers working with a mouse cancer model have found that insertion of the gene for a modified form of the enzyme Akt1 greatly increased the efficacy of experimental anti-cancer vaccines by extending the lives of the animals' immune system dendritic cells.

Akt1 (protein kinase B) is involved in cellular survival pathways through the inhibition of apoptotic processes. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer.

Investigators at the Baylor University College of Medicine (Houston, TX, USA) worked with groups of mice with either large pre-established lymphomas or aggressive B16 melanomas. They treated the mice by using an adenovirus vector to insert the gene for a modified form of Akt1. The new version of Akt1 was directed to specific sites on the membranes of dendritic cells.

Results published in the December 3, 2006, online edition of Nature Biotechnology revealed that the treatment enabled dendritic cells to survive significantly longer while promoting antigen-specific T-cell responses. The empowered dendritic cells could then orchestrate the elimination of tumors in the mice.

"The dendritic cells are the master switch in the immune system. They decide whether there will be a robust immune response or a tempered immune response to pathogens or cancer,” explained senior author Dr. David Spencer, associate professor of immunology at Baylor College of Medicine. "By keeping the dendritic cells alive longer, you extend the window of activation, promoting the desirable immune response, which in the case of cancer, is the expansion of T-cells. The longer your dendritic cells are alive and active, the more likely you are to expand the appropriate T-helper repertoire and ultimately the desirable cytotoxic T-lymphocytes.”



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Baylor University College of Medicine