Accession Number : ADA608505


Title :   Viral Immunotherapy to Eradicate Subclinical Brain Metastases


Descriptive Note : Final rept. 1 Sep 2011-28 Feb 2014


Corporate Author : PITTSBURGH UNIV PA


Personal Author(s) : Bergman, Ira ; Basse, Per


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a608505.pdf


Report Date : May 2014


Pagination or Media Count : 81


Abstract : To develop an immunologically based strategy for the treatment of breast cancer metastases to the brain (BM). Scope: To establish an animal model of BM and to demonstrate that anti-tumor memory T-cells can be activated to enter and destroy BM by the following methods: 1. Viral infection of BM by a recombinant replicating vesicular stomatitis virus (VSV) targeted to the Her2/neu receptor and causing oncolysis and cytokine expression and 2. Adoptive transfer of cytotoxic, cytokine-producing natural killer (NK) cells capable of accumulating in smaller metastases of the brain. Major Findings: A meningeal model was produced using the mammary cancer cell line, D2F2/E2. A parenchyma model was difficult to produce with this cell line. We showed that there is a blood-brain-barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier could be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cells transfer resulted in 89% cure of meningeal tumor in two different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the brain meninges of these same animals. A-NK cells traffic to brain tumors but less well than seen in pulmonary and hepatic tumors. Conclusions: These results support the hypothesis that a virally-based immunization strategy can be used to both prevent and treat brain metastases.


Descriptors :   *BRAIN , *BREAST CANCER , *CYTOKINES , *METASTASIS , *VIRUS DISEASES , CELLS(BIOLOGY) , CLINICAL MEDICINE , IMMUNOTHERAPY , INFILTRATION(FLUIDS) , LEUKOCYTES , LIVER , MAMMARY GLANDS , MEMORY DEVICES , MENINGES , NEOPLASMS , STRAINS(BIOLOGY) , VESICULAR STOMATITIS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE