TORONTO, ON / ACCESSWIRE / September 9, 2015 / Theralase Technologies Inc. ("Theralase" or the "Company") (TLTFF) (TSX Venture: TLT), a leading biotechnology manufacturer focused on commercializing medical technologies to eliminate pain and destroy cancer, announced today that its latest research demonstrates that its lead Photo Dynamic Compound ("PDC"), TLD-1433, in addition to being indicated for the treatment of Non-Muscle Invasive Bladder Cancer ("NMIBC"), may also be effective for the treatment of Muscle Invasive Bladder Cancer ("MIBC").
The latest research involved testing the Photo Dynamic Therapy ("PDT") of TLD-1433 in an orthotopic rat bladder tumour model.
Procedure:
- 1.5 million AY27 rat bladder cancer cells per milliliter were instilled in the sensitized rat bladder for one hour to allow the cancer cells to attach.
- Tumours required two to three weeks to grow to an appropriate size.
- TLD-1433 was intravesically infused into the rat's bladder at either 0.6 mgmL-1 (representative of human low dose) or 6.0 mgmL-1 (representative of human high dose).
- After one hour incubation, TLD-1433 was removed and the bladder was washed three times with sterile water to remove any unabsorbed TLD-1433 mirroring the proposed human clinical treatment.
- An optical fiber was inserted into the center of the rat bladder to deliver green laser light for PDT, at a dose of 90 Jcm-2 again mirroring the human treatment.
- Experiments were performed with drug only and light only controls to exclude any possibility that drug or light alone led to cell kill.
- The rats were sacrificed two days post-PDT and their bladders were sent to the histopathology lab for analysis.
Results (Representative of Human Low Dose):
- Five tumours treated with 0.6 mgmL-1 TLD-1433 (representative of human low dose) followed by PDT showed a strong response to the PDT with complete destruction of the tumour, with large areas of hemorrhage, necrosis (cell kill), and inflammation present throughout the whole depth of the tumour.
- Blood vessels of the submucosa, the muscle layer, and urothelium distal from the tumour area were unaffected by the PDT.
- Drug or light only controls showed no effect on the destruction of the tumour.
To view the images, click here.
Representative image of drug only control (A), light only control (B), and PDT treated (C) tumours. Upper row shows zoomed in view, with lower row showing full bladder thickness images. In all cases, the scale bar represents 100 µm. In the control tumours, tumour nuclei are well defined and closely packed. Two days after PDT treatment, the tumour mass shows widespread hemorrhage and inflammation, with an absence of cancer cells. The dark spots in the treated tumours are neutrophils responding to the widespread cell death and inflammation. Full thickness sectioning shows a completely necrotic (cell kill) tumour. The urothelium and the deeper muscle layers adjacent to the tumour are intact.
Results (Representative of Human High Dose):
Three tumours treated with 6.0 mgmL-1 TLD-1433 (representative of human high dose) followed by PDT showed a strong PDT specific response with complete destruction. TLD-1433 mediated PDT was able to induce full depth tumour necrosis (cell kill) across 2 to 3 mm deep tumours. Furthermore, TLD-1433 was able to induce full depth tumour necrosis in MIBC tumours, showing the wide versatility of TLD-1433 to treat bladder cancer across various progression stages.
To view the images, click here.
Representative images of control (A) and PDT treated tumours (B). Top row shows the macro image of the tumour, with the arrowhead pointing to the tumour. Bottom row shows histological sectioning of the tumours from the first row. All scale bars represent 1 mm. The control tumour shows unabated growth, reaching a thickness of 2 to 3 mm of highly packed proliferating cells. The tumour PDT treated with 6 mgmL-1 TLD-1433 shows full depth necrosis of the whole 2 to 3mm deep tumour. This necrosis is evident even at macroscopic observation, with the full tumour showing a deep red color.
To view the images, click here.
Representative image of MIBC in control (A) and PDT treated (B) bladders. In all images, the scale bar represent 0.5 mm. In the control, the highly proliferative cancel cells have infiltrated the deeper muscle layer in multiple locations. In the PDT treated bladder with 6.0 mgmL-1 TLD-1433, the tumour had invaded the muscle layer, but has become completely necrotic (cell kill) due to PDT treatment. The muscle and urothelial tissue flanking the tumor remains healthy and do not show signs of inflammation or necrosis.
Roger Dumoulin-White, President and CEO, Theralase stated that, "This is a very significant finding as there are 75,000 Americans and 8,000 Canadians diagnosed with bladder cancer every year. Of these individuals 70% present with early stage disease (NMIBC) with the other 30% present with more advanced cancer (MIBC). If this research can successfully be translated clinically, then not only will TLD-1433 be able to successfully treat NMIBC, it may also be indicated to successfully treat MIBC, without any impact to healthy tissue."
