Novel, cutting-edge cancer immunotherapy

Cancer immunotherapy is the next generation of cancer therapeutics, which aim to activate the body’s own immune system to identify, seek out and destroy cancer cells. Our immune systems 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. To read about some of these concepts and definitions, check out the FAQ.

 

One type of cancer immunotherapy, so-called oncolytic viruses, are genetically modified viruses that replicate in tumor cells and lead to their death. Lokon Pharma’s LOAd technology is a family of oncolytic viruses that are based on a common cold virus called adenovirus. Oncolytic viruses have the advantage of selectively replicating in tumor cells; in addition, the virus kills the tumor cell at the end of the replication cycle in order to release new virus particles.

 

LOAd viruses not only kill tumor cells directly, but these viruses also infect and modify the cells surrounding the tumor. LOAd-infected cells around the tumor express key immune-activating proteins (transgenes) from the LOAd virus, which primes the tumor environment and shifts it towards immune activation. This may be a key ingredient that enables the immune system to detect and disarm the tumor in order to mount a tumor-specific immune response.

 

Lokon Pharma’s unique technology not only utilizes oncolytic virus, but also immunostimulatory gene therapy. This means that each LOAd virus is genetically modified to contain different immune-activating genes (transgenes) that stimulate a variety of anti-tumor immune responses. The strategy behind transgene selection is based on tumor biology and also takes into account the mechanisms by which tumors evade our immune system and block anti-tumor immune responses. Read more about Lokon Pharma’s pipeline.

LOAd703 double-armed oncolytic adenovirus

Lokon Pharma’s first cancer therapeutic is a double-armed oncolytic adenovirus (LOAd703) that is currently being evaluated in clinical trials for the treatment of melanoma, pancreatic-, biliary-, colorectal-, and ovarian cancer. 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 immune-activating genes called TMZ-CD40L and 4-1BBL.

 

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. Read more about the ongoing LOAd703 clinical trials in Lokon Pharma's pipeline.

Reference list

Wenthe J, Naseri S, Labani Mothlagh A, Enblad G, Wikström KI, Eriksson E, Loskog A, Lövgren T. Boosting CAR T cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy. Cancer Immunol Immunother. 2021. Epub ahead of print.

 

Labani-Motlagh A, Naseri S, Wenthe J, Eriksson E, Loskog A. Systemic immunity upon local oncolytic virotherapy armed with immunostimulatory genes may be supported by tumor-derived exosomes. Mol Ther Oncolytics. 2021. 20:508-518.

 

Wente J, Naseri S, Hellström A-C, Jernberg Wiklund H, Eriksson E, Loskog A. Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40. Cancer Gene Ther. 2020. 27:948-959.

 

Eriksson E, Milenova I, Wenthe J, et al. Interleukin-6 signaling blockade during CD40-mediated immune activation favors anti-tumor factors by reducing TGF-beta, collagen type I and PD-L1/PD1. J Immunol. 2019. 202:787-798.

 

Eriksson E, Milenova I, Wenthe J, et al. Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus. Clin Cancer Res. 2017; 23(19):5846-5857.

 

Eriksson E, Moreno R, Milenova I, et al. Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment. Gene Ther. 2017;24(2):92-103.