X-Ray Psoralen Activated Cancer Therapy

• Published in: PLoS ONE 2016, Vol.11 (9), p.e0162078
• Main Authors: Oldham, Mark, Yoon, Paul, Fathi, Zak, Beyer, Wayne F, Adamson, Justus, Liu, Leihua, Alcorta, David, Xia, Wenle, Osada, Takuya, Liu, Congxiao, Yang, Xiao Y, Dodd, Rebecca D, Herndon, James E, Meng, Boyu, Kirsch, David G, Lyerly, H. Kim, Dewhirst, Mark W, Fecci, Peter, Walder, Harold, Spector, Neil L
• Format: Report
• Language: English
• Subjects: Analysis; Cancer; Care and treatment; Health aspects; Psoralens; Treatment outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162078

This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p