Transcript PPT
Nanoparticles for tumor immunotherapy Christine Pai Advisor: Davorka Messmer, PhD 2007 Calit2 UCSD Summer Undergraduate Scholar Research Program Introduction Currently, chemotherapy and radiation therapy are the most common forms of treatment for cancerous tumors. Unfortunately, these treatments lose their effectiveness over time and also have serious side effects, including immunosuppression, which can ultimately lead to death. The introduction of nanoparticles as a new cancer therapy offers new effective ways in targeting tumors and ultimately allowing our own natural immune system to destroy tumors. The nanoparticle is simple: The outside shell is lined with tumor targeting peptides and the inside is filled with immunostimulatory peptides that will enhance an immune response from the patient. In addition, the nanoparticle itself is safe for delivery and already FDA approved for human use. Characterization of the B16 Melanoma Cell Line In order to visualize the tumor progress of a mouse model in vivo, the selected tumor cell line will express luciferase, an enzyme that is capable of producing fluorescent color. The mouse will then be anesthetized and analyzed using the IVIS® Imaging System. University of California San Diego Immunostaining of tumor cryosections The mice are sacrificed and the tumor is extracted to freeze down. It will then be sliced into cryosections for further study with the help of pathologists. Project Plan •Determine to what extent intra-tumoral injection of “adjuvant” causes inflammation at the tumor site •Use nanoparticles for adjuvant delivery to the tumor Menon, C. et al. Clin Cancer Res 2001;7:3904-3911 Results Materials and Methods Currently the research project is still ongoing, however the following points have been accomplished: Hollow SiO2 Nanoparticles •Determination of most effective dose of the B16 Melanoma Cell line for the mouse model. •Perfected the use of ELISA and ELISPOT assays, which will measure the immune responses •Successful cloning of the chosen tumor antigens. Cloning Extensive work has been done to clone the tumor antigens that will be attached to the surface of the nanoparticle. The cloned tumor antigens (gp100 and MART1) will be used to stimulate specific immune responses. Future •We now need to deliver the signal to metastasis, which cannot be injected directly. •Delivery of inflammatory stimuli packaged into nanoparticles that will target the metastasized tumor via the vasculature (i.v. injection). •Our goal is to measure an inflammatory response, which will prep the tumor for a subsequent immune attack (cytolytic T cells, etc). Vector DNA Acknowledgements Recombinant DNA Molecule SEM photo of Core-shell silica nanoparticles SEM photo of Hollow silica nanoparticles Bacteria Special thanks to Davorka Messmer, Ginny Scott, and Calit2