Photocure ASA, the Bladder Cancer Company, announces the publication of new results from its exploratory research program in the journal Biomedicines, entitled “Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate (HAL) and Blue Light in an Orthotopic Model of Rat Bladder Cancer”. These results support initial pre-clinical data on the potential anti-tumor effect of HAL, which were presented at the BLADDR 2019 congress [https://photocure.com/news/photocure-new-data-from-hexvixr-trials-presented-at-the-bladdr-2019-congress-3457632].
The study objective was based on the hypothesis that the positive impact on long-term outcomes in NMIBC patients who had undergone Blue Light Cystoscopy (BLC) prior to cystectomy could be caused by a direct anti-tumor effect and/or activation of the immune system indicating an additional effect of Blue Light with HAL beyond pure detection. Therefore, as an exploratory preclinical study, the authors investigated whether intravesical administration of HAL followed by a diagnostic blue-light illumination-regime, aiming to mimic the one used currently in Photodynamic Diagnosis (PDD), could have anti-tumor and/or immune modulating effects as seen with Photodynamic therapy (PDT). In addition, it was explored if co-administration of a checkpoint inhibitor would increase the susceptibility to the PD-1/PD-L1 pathway inhibition thus increasing the anti-tumor effect. Over the years, Photocure has conducted a number of experiments on “mechanisms of actions” effects of HAL, as well as to see if there potentially are similar anti-tumor and immune modulating effects of PDD with blue light as reported with PDT. For this study, rats were treated with HAL and blue light in an orthotopic model of bladder cancer, and then subjected to histopathological analysis of the bladder samples and additional assessment of immune markers. Co-administration of HAL and blue light with a checkpoint inhibitor was further evaluated in this model aiming to assess for potentiation of anti-tumor effects when combined with an immunotherapy.
Results of the study demonstrated an anti-tumor effect of HAL and blue light when aiming to mimic the dosing regimen of a photodynamic diagnostic procedure (PDD) in an orthotopic bladder cancer model in rats.
The authors conclude “The anti-tumor effect is most probably pertaining to stimulation of the immune system as evident by tumor infiltration of CD3+ and CD8+ T-cells. These results support our hypothesis that the positive impact on patient outcomes observed in patients who had undergone BLC prior to cystectomy could be explained by systemic immune activation induced by HAL and blue light. Combination of HAL and blue light with intravesical anti-PD-L1 resulted in increased anti-tumor effects. Further studies are warranted to explore the long-term effects of HAL and blue light alone or in combination with checkpoint inhibitors which should extend to investigate any systemic (abscopal) effects. Intriguingly is also the idea that local treatment with HAL and blue light can prime an immune response with potential additional effect of checkpoint inhibitors.”