Theralase’s leading cancer-killing compound effective in preclinical models

by • March 5, 2018 • Drug Development, Feature Slider, Feature-Home, Featured-Slides-Home, OncologyComments Off on Theralase’s leading cancer-killing compound effective in preclinical models553

Theralase Technologies Inc. demonstrates that their leading compound, TLD-1443, for the destruction of lung cancer when used in conjunction with Rutherrin effectively kills the malignant cells in two preclinical animal models.

According to the American Cancer Society, lung cancer is the second most common form of cancer in adults next to skin cancer. Roughly 14 per cent of new cancers are diagnosed as a form of lung cancer. It is the leading cause of cancer death to men and women. Each year, more people die from lung cancer than breast, colon, and prostate cancers combined. Non-small cell lung cancer accounts for 80 to 85 per cent of patients.

There are different treatment options available dependent on the status of their diagnosis: surgery, radio frequency ablation, chemotherapy, targeted therapies, and immunotherapy. Lung cancer is aggressive and has a meager survival rate – more than half diagnosed with lung cancer rarely make it beyond the first year of diagnosis.

On their cellular surface of all cells, there are carrier proteins known as Transferrin Receptors (TfRs). The TfR’s main role is to link with the glycoprotein Transferrin (Tf) to allow the cell to absorb iron – an essential element required for energy production and metabolism.

Due to the high proliferation rate of cancer cells, they possess a greater quantity of TfRs and therefore absorb a greater quantity of iron than normal cells.

TLD-1433 is a Theralase patented ruthenium metal-based molecule. Ruthenium is a transitional VIII metal element (as is Iron and Osmium), in the periodic table that possesses similar chemical properties to iron.

Theralase has demonstrated that TLD-1433 bonds with transferrin to produce Rutherrin and in so doing, TLD-1433 is able to be selectively transported preferentially and in much higher quantities to cancer cells versus normal cells through the TfR.

Once inside the cancer cell, TLD-1433, when light activated, produces a vehement form of oxygen, known as Reactive Oxygen Species (ROS), that is able to effectively destroy the cancer cell from the inside out.

Theralase continued to research the efficacy of this drug to destroy non-small cell lung cancer by evaluating non-small cell lung cancer models that were developed underneath the skin and in tumours grown within organs.

In the subcutaneous (under the skin) tumour model, human NSCLC tumour cells (A549) were subcutaneously injected to induce a NSCLC tumour in mice. Once tumour presence was confirmed, the mice were injected intravenously with Rutherrin. Four hours post Rutherrin injection, mice were treated with Near Infra Red (NIR) light. Tumour samples forty-eight hours post treatment were analyzed to evaluate the efficacy of Rutherrin in the destruction of NSCLC tumours.

In the preclinical orthotopic (grown inside an organ) tumour model, that is clinically relevant, human NSCLC tumour cells were used to induce lung tumours in mice. Once tumour presence was confirmed, the mice were injected intravenously with Rutherrin. Forty hours post Rutherrin injection, the mice were intubated (a hollow tube inserted into the trachea) and NSCLC tumours were treated by intrathoracic light delivery. This treatment strategy is depictive of the clinical strategy to be used for human patients inflicted with NSCLC. Forty-eight hours post light activation, tumour samples were collected for analysis. Results demonstrate that light-activated Rutherrin treatment induced extensive areas of necrosis in NSCLC tumours.

“We are delighted to have demonstrated that light-activated Rutherrin is efficient in selectively destroying NSCLC cells in both a subcutaneous and an orthotopic animal model,” says Manjunatha Ankathatti Munegowda, Ph.D., DVM, research scientist at Theralase. “The orthotopic model is important in that it demonstrates the suitability of this treatment methodology to human clinical cases, as Rutherrin was delivered intravenously and the laser light was delivered directly into the lungs via fibre optics inserted through the trachea. This strong data will assist the Company to provide evidence to thoracic surgeons and oncologists to support a Phase Ib clinical study for NSCLC.”

In order to optimize the treatment in humans, the company will standardise the dose of Rutherrin and the fibre optic light delivery system to the NSCLC tumours to increase efficacy.

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