Harnessing Immunostimulatory Gene Therapy through Oncolytic Viruses
Cancer immunotherapy is the next generation of cancer therapeutics aiming to activate the body's own defense - the immune system - to seek and destroy cancer cells.
The immune system can recognize and fight cancer but cancer cells are shielded by the release of immunosuppressive substances and stroma, which reduce the normal immune attacks. Immunotherapy strengthens the immune system to regain capacity to destroy cancer cells.
The strategy of Lokon is to modulate the tumor microenvironment and simultaneously activate the immune system to attack the tumor. We aim to shift the suppressive environment to a Th1 (immunity) promoting milieu by targeting the CD40 pathway which affect stoma, tumor cells and the immune system. By gene therapy, immunostimulatory genes including our TMZ-CD40L, are inserted into the tumor area which cause a powerful inflammation leading to tumor cell destruction and activation of M1 macrophages, cytotoxic killer cells (CTLs) and NK cells.
Lokon Pharma develops unique immunostimulatory gene therapies based on our TMZ-CD40L platform. Eriksson et al Gene Ther 2017. Our first product into clinical trial is a double-armed oncolytic adenovirus (LOAd703) that is tested in patients with pancreatic-, biliary-, colorectal-, and ovarian cancer (NCT02705196, NCT03225989).
LOAd703 is an adenovirus serotype 5/35 armed with TMZ-CD40L and 4-1BBL. TMZ-CD40L and 4-1BBL are two potent stimulators of anti-tumor immunity by their capacity to activate dendritic cells and M1 macrophages to produce IL12, TNFa, IFNg and IL21, as well as to expand both memory T cells and NK cells. Further, TMZ-CD40L activates tumor stroma to participate in recruiting and activating anti-tumor immunity. Eriksson et al Clin Cancer Res 2017.
Our pipeline consists on a variety of LOAd family viruses. The idea behind the design and selection of transgenes is based on the biology of tumors and cross talk with the stroma.
The first patient has been enrolled in our Swedish trial (pancreatic-, biliary-, colorectal-, and ovarian cancer).
Our clinical trial for patients with pancreatic cancer in Houston has now treated the first patient!
EMA has granted Lokon an orphan designation status for LOAd703 immunotherapy for the treatment of pancreatic cancer.
FDA has granted Lokon an orphan designation status for LOAd703 immunotherapy for the treatment of pancreatic cancer.
Copyright ©2014, All other marks are the property of their respective owners.