The project goals are 1) to develop biocompatible nanoparticles (NP) bearing Pattern Recognition Receptor (PRR) molecules, i.e., agonists for Toll Like Receptors or C-type Lectin Receptors, 2) to determine if these NP- PRR differently affect activation of dendritic cells (DC), 3) to determine if the differently activated DC then influence the generation and functionality of T effector cells, and 4) to evaluate the alloreactive CTL and the autologous tumor associated antigen (TAA)-directed CTL in the GL261 mouse glioma model, where the tumor cell inoculum either is or is not enriched for brain tumor stem cells (BTSC). The latter goal will allow for a determination of BTSC immunosensitivity/immunoresistance. The cancer immunotherapy approach will: "Use various NP-PRR (CpG DNA, imiquimod, LPS and mannosylated BSA) that will be components of a biocompatible PLGA carrier matrix already approved for clinical use to stimulate DC to variable activation states. In some experiments complex NP-PRR will also contain tumor associated antigens (mEphA2, hgp100, mTRP-2 and GARC-1) " Use conventional and Flt3 ligand DC derived from immature bone marrow (BM) as precursor cells " NP-PRR activated DC will then be used to stimulate alloreactive or autologous naive T cells to effector cytotoxic T lymphocytes (CTL) "NP-PRR stimulated DC and subsequently stimulated CTL will be functionally and phenotypically characterized in vitro."Stimulated alloreactive CTL or TAA-directed CTL will be functionally and phenotypically characterized for their antitumor effects after their adoptive transfer into mice bearing serum-cultured GL261 or the neurosphere-cultured counterpart.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA154256-05
Application #
8704325
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Welch, Anthony R
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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