Exogenous Induction of Alzheimers disease

Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-ß (Aß)–containing brain extracts from humans with Alzheimer's disease or ß-amyloid precursor protein (APP) transgenic mice induced cerebral ß-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Aß immunodepletion, protein denaturation, or by Aß immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Aß strains with varying biological activities reminiscent of prion strains.

Source:
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host. Melanie Meyer-Luehmann et al. Science 22 September 2006: Vol. 313. no. 5794, pp. 1781 - 178

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Cancer regression using genetically engineered lymphocytes

Using adoptive transfer of lymphocytes given after host immunodepletion it is possible to mediate objective cancer regression in patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Using a retrovirus encoding a T cell receptor, we report here the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood. Adoptive transfer of these transduced cells in fifteen patients resulted in durable engraftment at levels exceeding ten percent of peripheral blood lymphocytes for at least two months post infusion. We observed high sustained levels of circulating, engineered cells at one year post-infusion in two patients, that both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

Source:
Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes
Richard A. Morgan, Mark E. Dudley, John R. Wunderlich, Marybeth S. Hughes, James C. Yang, Richard M. Sherry, Richard E. Royal, Suzanne L. Topalian, Udai S. Kammula, Nicholas P. Restifo, Zhili Zheng, Azam Nahvi, Christiaan R. de Vries, Linda J. Rogers-Freezer, Sharon A. Mavroukakis, and Steven A. Rosenberg
Published online 31 August 2006 [DOI: 10.1126/science.1129003] (in Science Express Reports)

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