(Sunday, 7/29/2018) 3:00 PM - 6:00 PM
Room: Exhibit Hall
Purpose: Cutaneous metastasis is often the penultimate harbinger of death for many breast cancer patients. New therapy approaches are urgently needed for such patients. The overall goal of this project is to develop a new Subcutaneously Modulated Abscopal Response Radiotherapy (SMART) approach for treating subcutaneous metastasis in such a way as to generate the immune-mediated abscopal effect, towards elimination of the cutaneous metastasis and other cancer cells elsewhere in the body.
Methods: In in-vitro studies, 1000 cells/well of human triple negative breast cancer cells (MDA-MB-436) were seeded in 6-well plates. 24-hours after seeding, the cells were treated with high atomic number nanoparticles to generate immunogenic high linear energy transfer (LET) damage to the cancer cells during 220 kVp (skin) radiotherapy (RT) at varying doses using a small animal radiation research platform (SARRP), followed by Clonogenic assay. Finally, microneedles that can be administered as a painless skin patch were developed for incorporating a payload of nanoparticles with immunoadjuvants for use in sustained delivery of the payload subcutaneously to prime the abscopal effect.
Results: High-Z nanoparticles along with RT treatment showed a synergistic effect compared to separate treatment of either one alone. For example, survival at 2Gy using 0.25 mg of gold nanoparticles was 20% compared to about 70% when using RT alone. Results for microneedles showed excellent prototypes made of biocompatible FDA approved PLGA polymers, with demonstrated potential for sustained release of nanoparticles and other payloads in-vitro and in-vivo.
Conclusion: The results combined with preclinical study analysis justify further work developing the SMART approach for treating breast cancer patients with cutaneous metastasis using targeted kilovolt energy radiotherapy. Photons with such energies can induce micrometer-range high LET photo-auger electrons, which are highly immunogenic to prime the abscopal effect enabling both local and remote tumor cell kill.
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