Lokon Pharma | Our Solution

Cancer immunotherapy

The immune system can recognize and kill microbes but also damaged or malignant cells like cancer cells. However, cancer surrounds itself with immunosuppressive cells and molecules that prevents the immune cells to function properly. The cancer “escapes” immunity.

Our solution stimulates the body's own immune system to seek and destroy cancer cells. It modifies the cancer cells and the cells surrounding the tumor to shift towards immune activation. Our solution is based on the transfer of immunostimulatory genes to the tumor microenvironment using oncolytic viruses as gene transfer vehicles.

Besides providing immune stimulation, our tumor microenvironment (TME) gene engineering vectors selectively replicate and kill the tumor cells in the end of the replication cycle, in a process called oncolysis.

What is immunotherapy?

Cancer immunotherapy is the new generation of cancer therapeutics, which aims to activate the body’s own immune system to identify, seek out and destroy cancer cells.

Our immune system can recognize and fight cancer, but cancer cells often escape detection and destruction by the immune system by releasing immunosuppressive substances that inhibit immune responses.

The aim of cancer immunotherapy is to both disarm the tumor’s ability to block an immune attack as well as to activate anti-tumor immune responses.

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Immunostimulatory gene therapy

One type of cancer immunotherapy is called immunostimulatory gene therapy.

By genetic engineering of the tumor to express human immunostimulatory genes, it will attract immune cells and support them with activation signals leading to tumor immunity.

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What is an oncolytic virus?

An oncolytic virus is a recombinant virus that has been genetically modified in a laboratory to specifically replicate in tumor cells. At the end of the replication cycle, the oncolytic virus kills the tumor cell to release new virions (virus particles).

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The LOAd technology

Lokon Pharma’s LOAd technology is a tumor microenvironment (TME) gene engineering vector family based on oncolytic viruses. The viral gene vehicle is a common cold virus called adenovirus.

Each LOAd virus is genetically engineered to encode different immunostimulatory genes that induce tumor stroma inflammation to activate anti-tumor immune reactions with subsequent tumor immunity. It can be described as an “in situ vaccination”.
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The strategy behind the selection of immunostimulatory genes inserted into LOAd gene vehicles is based on tumor biology while taking into account the mechanisms by which tumors evade our immune system and block anti-tumor immune responses.

Lokon’s viruses, LOAd

Our unique technology not only utilizes oncolytic viruses to induce oncolysis (tumor cell death), but also immunostimulatory genes that are transferred to the tumor and its microenvironment via the LOAd viruses.

Lokon’s virus is unique because it can transfer immunostimulatory genes both to the tumor-promoting stroma and to the cancer cells while oncolysis is restricted to cancer cells.

How?
Lokon utilizes oncolytic viruses as gene vehicles. The viruses are also armed with immunostimulatory transgenes.

Upon infection of tumor cells the virus will induce expression of human immunostimulatory transgenes, which will lead to activation of anti-tumor immunity. The virus will also initiate production of new viral particles that eventually induce oncolysis of the tumor. Normal cells in the tumor microenviroment will express the immunostimulatory transgenes after infection, but the replication is poor and, hence, the virus cannot induce lysis.

Expression of immunostimulatory transgenes in both cancer- and normal cells may lead to an enhanced, robust, and prolonged immune response compared to expression merely in cancer cells.

LOAd703

LOAd703 is our first gene therapy being tested in clinical trials and it is currently being evaluated in pancreatic cancer, ovarian cancer, colorectal cancer, biliary cancer and melanoma.

Inside the LOAd virus

The LOAd703 virus is a double-armed oncolytic adenovirus. LOAd703 (adenovirus serotype 5/35) has the ability to kill tumor cells, as well as enabling both cancer cells and surrounding cells to express two potent immunostimulatory genes called TMZ-CD40L and 4-1BBL.

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A deeper look into LOAd

TMZ-CD40L and 4-1BBL are potent stimulators of anti-tumor immunity that activate key immune cells, like dendritic cells and M1 macrophages, to produce potent cytokines such as IL12, TNFa, IFNg and IL21.

In turn, these so-called Th1 cytokines expand NK cells and memory T cells, key players in mounting and sustaining anti-tumor immune responses.

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