Mastering tissue specific RNA delivery for efficient cancer immunotherapy
We are dedicated to developing tissue specific RNA delivery for efficient cancer immunotherapy
Technology
RNA therapeutics have come to stay
mRNA (messenger mRNA) helps produce therapeutics directly on site, in our own tissues and cells, without the need to manufacture these in industrial factories. One can consider mRNA as a molecular message that contains the construction plan of a therapeutic protein.
Immune system is a defense mechanism that has already been built into our body, it has amazing ability to recognize foreign and malignant objects, without the need for intervening with chemically synthesized toxic compounds.
The combination of these two—therapeutic mRNA and activation of the immune system—underlies the use of mRNA for cancer immunotherapies.
Cancer immunotherapy
Cancer immunotherapy means helping our immune system to fight cancer, it provides advantages over traditional chemotherapy in that instead of injection of toxic chemical compounds, the body’s native defense mechanism is allowed to kill any abnormal tissues. In addition, activated immune system offers long term protection against any recurrence of cancer.
There are three main approaches how we can activate the immune system. But the first question is, why does our immune system need any help? The answer is, it is difficult for the immune system to detect cancer because malignant cells have ways of avoiding (escaping) the immune system. This is depicted in the right side of the figure below where cancer is undetected and can grow uncontrollably.
Immune checkpoint inhibitors
The first generation of immunotherapeutics, called immune checkpoint inhibitors, are removing the block, making cancer visible to the immune system. This is depicted in the rightmost section of the figure below. Unfortunately, this approach works only in less than half of the patients, and only in case of some cancer forms.
Ex vivo CAR T
Therefore, in order to achieve successful immunotherapy, immune cells need to be activated, or “told”, which cells to hunt. There are two general ways of achieving that, depicted in the middle part of the figure. CAR T cell approach manipulates the killer immune cells in our bodies and these cells are taught to recognize cancer. The challenge is that these cells need to be removed from the patient, engineered in a laboratory, and then put back in the patient, which is technically very complicated procedure.
mRNA -based immunotherapies
mRNA uses natural way of activating the immune system. There are specific immune cells in our body—the antigen presenting cells—that are looking for foreign signals in our body and then teaching these signals to another type of immune cells—the killer T cells. Instead of taking the T cells out from the patient, we can let the antigen presenting cells do their job and convey the needed message. That is exactly how Vectiopep works—it conveys the message to the antigen presenting cells, which activate the killer T cells.
Vectiopep technology
Vectiopep is focusing on selective activation of the patient’s innate immune system to fight cancer. We achieve this by transporting the molecular message (mRNA) very selectively into the immune cells in the patients’ body. Because Vectiopep achieves unprecedented selectivity in RNA delivery into immune cells, it opens new possibilities to treat cancer by “telling” our immune cells which malignant cells to hunt and kill.
Our uniqueness stems from the chemical composition: Vectiopep is a cell penetrating peptide (CPP) that has specifically been designed for potent, selective and nontoxic transport of therapeutics into the patients’ cells. Vectiopep is unique in its ability to selectively translocate mRNA into the immune cells. This is a remarkable feat, because the transport of mRNA is in general notoriously challenging, and in most cases, only the cells in our liver tissue can be targeted. Vectiopep propensity to find and target the immune cells opens up the possibilities to widen the scope of mRNA therapeutics and offer new solutions to treating cancer.
The development of Vectiopep started with the generation of a library of cell penetrating peptides and we started specifically selecting for the ability to transport mRNA into the immune organs. By iterative design (the best performers were selected and further modified), we screened for this specific property and finally selected a small number of peptide candidates with superior activity towards immune cells.
Indeed, beyond selective transport of mRNA, Vectiopep technology specifically activates our antigen presenting cells (dendritic cells) and killer T cells. We have proven in preclinical models that transport of mRNA that contains information about tumor antigen is very effectively activating immune system and inhibiting cancer growth.
Delivery technology
Nucleic acids by itself are not capable of reaching human cells and tissues and that is why delivery system is needed. Vectiopep spontaneously wraps mRNA into nanoparticles, protecting them from degradation that would otherwise occur in our organism.
Precision delivery
Vectiopep has extremely high preference towards lymphoid tissues, being able to transport >99% of the mRNA into spleen (by comparison, the industry standard LNP only transports <3% of the mRNA into spleen, whereas 97% accumulates to liver).
Nanoparticle delivery
The cell penetrating mechanism of Vectiopep-mRNA nanoparticles allows overcoming of serious biological barriers and achieve the transport of mRNA specifically into the antigen-presenting cells.
Tumour antigen cells activation
While reaching spleen, Vectiopep takes mRNA into the dendritic cells, where ribosomes are translating the message into the tumour antigen that is to be presented to the T-cells.
