What Is Telomerase ? Telomerase is a self enzyme that lengthens telomeres and extends cellular proliferation capacity. Its discovery was rewarded by the Nobel Prize of Medicine in 2009. Sometimes, precancerous cells manage to reactivate telomerase, and thus can proliferate indefinitely. They can now form tumors and metastasis. Normally telomerase is only transiently present at the fetal stage to replenish telomeres and reload all your regeneration capacity for your all life time. After birth, telomerase is shut down, and telomeres slowly shorten at each cellular division. Telomerase is normally not active at the adult stage. This prevents precancerous cells to transform into large tumors. However telomerase is abnormally reactivated in 90% of human cancers where it supports the unlimited proliferation of cancer cells. Telomerase is a universal cancer target

What is Cancer Immunotherapy ? Cancer immunotherapies are treatments based on the activation of the immune system to cure cancer. This was rewarded by the Nobel Prize of Medicine in 2018. When a cancer has accumulated far too many mutations, the immune system can start to see the cancer as non-self and attack the tumor with the help of anti-PD1. However, in most cases, cancer is still too similar to the self to be detected as non-self, and tumors are tolerated by the immune system which does not attack them. At Telomium, we develop a new kind of “vaccine” to reprogram the immune system and make it believe that cancer self-elements (like telomerase) are dangerous virus. Then, the immune system destroys all cells (the cancer cells) containing the target, like if there were infected cells.

An Introduction to the Immune System. The immune system prevents pathogens (like virus, bacteria, fungus…) to invade the human body. The immune system is pretty similar to an army. It contains multiples weapons to destroy foreign invaders. The immune system produces antibody to neutralize pathogens at distance, but it also kills cells that have already been infected. Indeed, each cell of the human body continuously displays degradation products from its internal activity at its surface (through the HLA/MHC system). T lymphocytes scan the surface of cells to detect foreign elements. If a non-self peptide is found on a cell, the cell is considered infected by a putative virus and is therefore killed by T-cells to prevent further spreading of the infection

The Idea of a Therapeutic Cancer “Vaccine”. The immune system is made to tolerate the self and to destroy the non-self (pathogens). Vaccines can activate the immune system; however, current cancer vaccines are poorly efficient against cancer, as cancer comes from the self. A tumor is not a foreign element and is therefore tolerated by the immune system. Vaccination is the greatest success of medicine. If vaccines have been very efficient at inducing antibodies to prevent new infections, until now, vaccines are less efficient at inducing T-cell immunity required to kill cancer cells, because tumors targets are self-antigens that have already been tolerized (contrary to a foreign antigen found in virus, bacteria or other pathogens). If one had the technology to make the immune system believe that a self element of the tumor (like telomerase or another tumor antigen) is not from the self, but is a virus, the T lymphocyte would then destroy cancer cells now seen as cells infected by a putative virus. To become really efficient cancer vaccine need to break immune tolerance. In some instances, the immune system can become deregulated and attack the self. This occurs in autoimmune diseases. Even though all self-antigens are normally tolerized, ribonucleoproteins are self-elements commonly known to break immune tolerance (to the self) and cause various autoimmune pathologies.

Ribonucleoprotein Vaccines. Ribonucleoproteins are macromolecules especially difficult to produce and need a special engineering to become highly effective as therapeutic cancer vaccines. Telomium has a unique knowledge in ribonucleoprotein production and has developed proprietary new technologies to break immune tolerance with ribonucleoproteins against a variety of cancer targets or other pathologies, surpassing all current vaccine technologies: mRNA vaccines, Viral vaccines, DNA vaccines, Protein/peptides vaccines, DC vaccines…

Ribonucleoproteins Break Immune Tolerance. Ribonucleoproteins are self-macromolecules complexes that are often mistakenly taken for virus by the immune system and become targets in various autoimmune diseases. Ribonucleoproteins released outside cells are interpreted by the immune system as a virus escaping the classical immune response, thus requiring a more profound and diverse immune response. Ribonucleoproteins are protein-RNA complexes delivering a temporospatially coordinated activation of a danger signal (by their RNA part) and presentation of the antigen (by their protein part) in the same phagosome, therefore more efficiently mimicking a viral infection, that any other vaccine technologies (even mRNA or viral vectors). The alarming signal provided by released ribonucleoproteins is so high that the immune system now attacks any cells containing the ribonucleoprotein, even if the ribonucleoprotein is a part of the self. This breaks immune tolerance. Ribonucleoproteins have the unique ability to induce the dual antigen receptor/Toll-like receptor signaling in B cells that diversifies the T cell response to novel epitopes, a key feature unmet by any other vaccine technologies (mRNA, DNA, viral vectors, peptide, proteins…). The dual BCR/TLR signaling induced by the ribonucleoprotein in the endosomes of B cells transforms B cells into prominent antigen-presenting cells (APC), now delivering unique activation signals to T cells (unreached by any other APCs, even dendritic cells). B cells activated by ribonucleoproteins antigens diversify the T cell response and break tolerance by promoting epitope spreading to untolerized epitopes. Ribonucleoproteins can therefore be developed as highly potent “vaccines” to reprogram the immune system and make it attack a specific part of the self. (ex: telomerase in cancer)..

What is Cancer ? The human body is made of cells. Each cell contains DNA. The DNA codes for a program that controls the functions of each cell. When too many mutations occur in the DNA of a cell, the genetic program regulating cellular proliferation can be damaged. If this happens, the cell becomes crazy and starts to proliferate and invade the body. This can ultimately lead to cancer.

What are Telomeres ? If the accelerator of a car is blocked and the brake is also broken, the damaged car runs wild but hopefully it will stop when all its fuel is over. Similarly, cells bearing damaged DNA proliferate abnormally, but their proliferation “burn” their telomere reserve, and the cells ultimately stop growing when their telomeres are too short.. Each adult cell can replicate only for limited number of times (50 to 70 times). This is a safeguard mechanism to prevent abnormal cells to form tumor

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