Scientists seeking to harness the power of the immune system to eradicate brain tumors face two major hurdles: recruiting key immune cells called dendritic cells into areas of the brain where they are not naturally found and helping them recognize tumor cells as targets for attack.
Researchers at Cedars-Sinai Medical Center, however, have identified a sequence of molecular events that accomplish both objectives. Their findings, based on laboratory and animal studies, appear in the Jan. 13 issue of PLoS Medicine, an open-access online journal of the Public Library of Science.
The Cedars-Sinai team discovered that a protein – HMGB1 – released from dying tumor cells activates dendritic cells and stimulates a strong and effective anti-tumor immune response. HMGB1 does so by binding to an inflammatory receptor called toll-like receptor 2, or TLR2, found on the surface of dendritic cells.
Here is part of the abstract of the research paper. Click thru to read the full paper.The researchers delivered gene therapy into the tumor mass and provoked an immune response.
Using a combined immunotherapy/conditional cytotoxic approach that utilizes adenoviral vectors (Ad) expressing Fms-like tyrosine kinase 3 ligand (Flt3L) and thymidine kinase (TK) delivered into the tumor mass, we demonstrated that CD4+ and CD8+ T cells were required for tumor regression and immunological memory. Increased numbers of bone marrow-derived, tumor-infiltrating myeloid DCs (mDCs) were observed in response to the therapy. Infiltration of mDCs into the GBM, clonal expansion of antitumor T cells, and induction of an effective anti-GBM immune response were TLR2 dependent.
But can the gene therapy get delivered with sufficient specificity for cancer cells that non-cancer cell loss is minimized?
Brain cancer is especially challenging because we can't afford to cut out large amounts of brain tissue in order to get the tumor. We need to find ways to very very selectively target just the cancer cells. That is especially true for brain tumors.
|Share |||Randall Parker, 2009 January 15 12:02 AM Biotech Cancer|