Valo Therapeutics Aims to Improve Personalized Immunotherapy With a New Tech
Valo Therapeutics Oy (ValoTx), the developer of antigen-coated oncolytic viruses and vaccine vectors as therapeutic vaccines against cancer and infectious disease, announced the exclusive licensing of intellectual property rights for the PeptiCHIP technology, developed at the University of Helsinki, Finland. This technology is expected to speed up identification of tumor antigens (including the group of neoantigens) for the development of new cancer immunotherapies using Valo’s existing technologies.
Cancer immunotherapy is a multi-directional group of approaches which share the same core principle: tumor is destroyed using the forces of the human immune system. Basically, depending on how the immune system is exploited, cancer immunotherapies are divided into active and passive.
In case of active immunotherapy, the given treatment aims to stimulate the host’s immune system, so to say “teach” what to attack and enhance the attack. This group of approaches includes cancer vaccines, immuno-modulators and check-point inhibitors. Why is it working in case of cancer? Tumors often have a hostile immunosuppressive microenvironment, so without the additional boost -- the immune system is blind and weak around the tumor, but active cancer immunotherapy tries to address this issue.
On the other hand, during passive cancer immunotherapy the immune agents are given to patients. This strategy works great with CAR-T cells for blood cancers, having already multiple FDA-approved treatments. Also passive immunotherapies include monoclonal antibodies binding cancer cells, and oncolytic viruses. To look into more details for the last mentioned class -- oncolytic viruses, it is also fair to classify them as both passive and active immunotherapy at the same time.
At first, the tumor is attacked with the specifically targeted viruses, which causes the cancer cells lysis (breakage of the cell membrane). Consequently, this leads to the local inflammation, where the immune cells are recruited to clean up the mess, and to pick up new antigens in the process. So, after being at first the passively acting viruses, they consequently stimulate active immune response. This ambidextrous mechanism of action is an attractive strategy for so-called “cold tumors” -- the ones which can’t be reached with the immune system without specific interventions.
The lead program of ValoTx called PeptiCRAd is based on oncolytic adenovirus, loaded with tumor specific peptides. To discuss both sides of the coin, the oncolytic virus strategy in general has a unique mechanism of action, which can target “cold tumors”, induce a strong immune response and effectively destroy the cancer cells. On the other hand, oncolytic viruses are known to be able to induce side effects as a result of activity towards healthy cells. Also, the immune response can be too strong, causing a severe inflammation and an extensive antibody production towards the virus particle itself, consequently neutralizing it.
The schematic demonstration of the PeptiCRAd platform principle, based on oncolytic viruses. Image Credit: ValoTx
Another limitation of the oncolytic viruses is the choice of antigens they are loaded with: it should be carefully selected, and there is a limited number of antigens which are suitable. It is possible to speculate that the PeptiCHIP technology, acquired by ValoTx, is a strategic tool to partially overcome this limitation and determine potential antigens more effectively.
PeptiCHIP consists of a microfluidic chip for identification of neoantigens, coupled with a software algorithm that identifies immunogenic peptides. According to the developers, the device complemented with software form an easy-to-use lab tool that enables the fast and accurate identification of tumor antigen profiles.
Addressing current neoantigen platform limitations, PeptiCHIP technology was designed to ease the pain by facilitating neoantigen identification at a lower cost and requiring less tumor material compared to some alternative methods. This might lead to faster tumor antigen identification in standard biopsy clinical workflows, if successfully validated for the clinical usage.
Paul Higham, CEO of ValoTx, commented:
“Precisely knowing the antigen profile of a tumor is crucial in developing new and effective immunotherapies in the treatment of cancer and particularly so when developing a personalized approach. PeptiCHIP enables us to identify these antigens faster than existing technologies and, in combination with our lead delivery platform, PeptiCRAd, we see significant potential for the development of personalized cancer immunotherapies across a wide range of cancers both for our partners and in-house programmes.”
To look more into the details of mechanism of action, according to the results published in “PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification” the technology is based on the more efficient capturing of the peptide antigens from the tumor lysates. According to the researchers, the microfluidic chip binds the HLA peptides throughout the biotinylated pan-HLA antibodies, which are anchored to streptavidin. Here HLA means the human leukocyte antigen (HLA) system, which is also known as the major histocompatibility complex (MHC) in humans. To break it down, HLA peptides are short amino acid sequences which are presented on the cell surface, manifesting some immunogenic potential.
A schematic overview describing the microchip methodology for antigen discovery. Image Credit: ACS Nano, 2021, DOI: 10.1021/acsnano.1c04371
It is important to mention, that even though PeptiCHIP technology can assist with the identification of tumor immunopeptidome, the captured peptides still require mass-spectrometry analysis and further in vitro tests for the antigen validation. Additionally, MHC-I complex presents not only tumor-specific antigens (also referred as “neoantigens”) but the soup of various peptides, meaning that PeptiCHIP would capture the wide set of irrelevant for immunotherapy peptides which then need to be excluded by the bioinformatic analysis. Overall, the technology is still to be validated for the clinical samples, which is the next milestone for ValoTx.
To zoom out, the immunopeptidome study used by PeptiCHIP is one of the antigen-identification strategies, which is generally not widely used for the neoantigen identification. It can have some advantages by showing the fraction of already presented peptides on the cell surface, but defining their exclusive specificity for the cancer cells is a remaining challenge.
The most common strategy for neoantigen identification remains to be DNA and RNA sequencing, providing the information about tumor-specific mutations, followed by the prioritization of those which are more likely to be recognized with the immune system. This requires the heavy computational data processing and machine learning approaches, as it was summed up in a recent Nature paper, but at the same time it reveals the valuable sequence-specific insights, unavailable with alternative methods.
