COVID-19 Vaccine Vector Repositioned for Cancer and Gene Therapies
Developed from COVID-19 vaccine research, gorilla vectors are well-suited for a range of therapeutic applications.
As gene and cell therapies mature, developers are increasingly looking beyond existing delivery systems to address challenges around targeting, immunogenicity, manufacturability, and cost.
Dr. Angelo Raggioli, head of technology development at ReiThera, leads platform strategy across vaccines, gene therapy, and oncology, and is all too familiar with these barriers.
Recognized for advancing a gorilla-derived adenoviral vector into clinical-stage COVID-19 and HIV vaccines, Raggioli and his team are now extending this strategy into broader applications—revealing unexpected advantages along the way.
Technology Networks spoke with Raggioli at Advanced Therapies UK, where he explained how the gorilla adenovirus behaves differently from human vectors, how the respiratory environment offers opportunities for targeted gene therapy, and why misconceptions around adenovirus-associated thrombosis warrant a more nuanced scientific discussion.
From vaccines to a multi-modal therapeutic platform
How is ReiThera redefining its platform strategy beyond vaccines and into gene therapy and oncology?
ReiThera’s mission was originally vaccine-driven, focusing on the isolation of a non-human primate adenovirus to achieve increased potency and low seroprevalence.
Seroprevalence
Seroprevalence refers to the proportion of a population that has detectable antibodies against a specific pathogen or vector. In the context of vector-based vaccines, low seroprevalence is desirable, as pre-existing antibodies can neutralize vectors, thus reducing vaccine efficacy.
“Historically, we identified the gorilla adenovirus and made a product—the COVID-19 vaccine,” Raggioli said.
Rather than continuing to develop single products and take them to market, the team is now focusing on building modular, reusable vector technologies. “Now, we are developing the technology up to a certain level and offering it as a platform that others can use,” Raggioli explained.
The result? Therapeutic developers can adapt these technologies for various use cases, including infectious diseases, oncology, and lung-targeted gene therapies.
This shift could facilitate:
- Reduced need for extensive vector redesign across indications
- A focus on enabling partners rather than competing with them
- Increased regulatory readiness and commercialization viability
Harnessing tumor selectivity for oncological applications
How does the gorilla adenovirus achieve tumor selectivity without extensive genetic engineering?
Notably, the gorilla adenovirus can enter cells and produce antigens for cell-surface expression, which is conducive to its role as a vaccine vector. But crucially, healthy cells do not support its replication.
Raggioli describes the underlying mechanism as straightforward but powerful: many cancer cells have dampened innate immune defenses, allowing viral replication that would otherwise be blocked in healthy cells.
This may confer a level of intrinsic tumor selectivity, as suggested by preclinical preprint data, reducing the need for extensive genetic modifications typically required for oncolytic viral therapies.
Oncolytic viral therapies
A type of immunotherapy that uses viruses or vectors designed to infect and replicate within cancer cells, leading to tumor cell lysis.
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This contrasts with human adenovirus serotype 5 (Ad5)—the industry benchmark for oncolytic viral therapies—which requires extensive genome engineering to restrict replication to tumor tissue.
“With Ad5, you have to engineer selectivity,” he said. “With this vector, selectivity is already there. Of course, we can further engineer it if needed, but the baseline behavior is very different.”
Why this matters for oncolytic development:
- Tumor selectivity is intrinsic
- Reduced engineering is required
Inherent lung tropism strengthens respiratory gene therapy potential
How does lung tropism expand the potential of adenoviral vectors for gene therapy and oncology?
Beyond tumor selectivity, the gorilla adenovirus also exhibits a distinct biodistribution profile, positioning it as a strong candidate for respiratory indications such as lung cancer and cystic fibrosis.
“The benchmark Ad5 goes to the liver when given systemically; our gorilla adenovirus naturally goes to the lung.”— Dr. Angelo Raggioli
This difference is therapeutically meaningful, as natural lung tropism results in higher effective doses in the lungs which should theoretically reduce exposure elsewhere in the body.
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Tropism
In this context, tropism refers to the tendency of a viral therapy to localize to or target a particular tissue.
In the context of respiratory diseases, the gorilla adenovirus not only delivers gene therapy to where it is needed, but it also has the capacity to transport and deliver exactly what is needed.
Unlike adeno-associated virus (AAV) vectors, which are constrained by a ~4.7–5.0 kb capacity limit, adenoviruses can accommodate tens of kilobases of genetic material.
“If you want to deliver a large gene, like a cystic fibrosis transmembrane conductance regulator, it simply doesn’t fit into AAV,” Raggioli noted. “Our vector can handle that.”
Key advantages of lung tropism in respiratory applications include:
- Preferential delivery to pulmonary tissue
- Compatibility with large-gene payloads
- Potential for reduced off-target effects
Turning tumors into local monoclonal antibody factories
How can adenoviruses be engineered to deliver complex payloads such as monoclonal antibodies?
One of the most forward-looking applications Raggioli envisions is in situ monoclonal antibody production.
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In this approach, an oncolytic adenovirus is engineered to carry a gene encoding a therapeutic antibody or cytokine. Once the virus infects tumor cells, those cells begin producing the therapeutic protein.
This offers localized therapy, Raggioli explained: “The virus replicates only in the tumor and, at the same time, the tumor cells become biofactories producing the monoclonal antibody.”
This offers several potential advantages over systemic antibody administration:
- Reduced systemic exposure and toxicity
- Increased concentration and extended functional half-life at the tumor
Oncolytic viral therapies are re-emerging
Why is there renewed interest in oncolytic viruses, particularly in combination with CAR T therapies?
After years of fluctuating interest, viral oncolytic therapies are attracting attention once again. They are increasingly recognized as a promising strategy for advancing cancer immunotherapy and overcoming a long-standing challenge: solid tumors.
“CAR T works very well in blood cancers, but much less in solid tumors,” Raggioli said. “The tumor microenvironment is a major barrier.”
By degrading extracellular matrix components and increasing immune cell tumor infiltration, oncolytic viral therapies can alter this microenvironment, making solid tumors more accessible to CAR T cells.
“Now there is renewed interest in oncolytics because they can be combined with CAR T,” he said.
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This realization has prompted investment across the sector, with stakeholders hopeful that combination therapies could be the key to successfully applying immunotherapy to solid tumors.
Drivers of oncolytic investment include:
- Renewed interest in solid tumor CAR T with evolutions such as armored CARs
- Microenvironment disruption with oncolytics offers solutions to solid tumor immunotherapy
Addressing adenovirus-associated thrombosis misconceptions
What misconceptions exist around adenoviral vectors and thrombosis risk?
One of the most persistent concerns surrounding adenoviral vectors is the risk of vaccine-induced thrombotic events, particularly following COVID-19 vaccination with ChAdOx1 and Ad26 vectors.
“The misconception is that all adenoviruses cause thrombosis. That’s simply not supported by the biology.”— Dr. Angelo Raggioli
Emerging hypotheses suggest that cases of thrombosis may be linked to somatic hypermutation phenomena associated with specific adenovirus species, rather than adenoviruses as a class.
Somatic hypermutation
In the context of thrombosis, somatic hypermutation refers to the dysregulation of a normal antibody‑maturation process that may generate antibodies against platelet factor 4 (PF4), a driver of coagulation. Hypotheses suggest that certain adenoviral vaccine vectors may create an immune environment that inadvertently drives this process, leading to pathogenic anti‑PF4 antibodies and thrombotic events. These events are rare.
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Notably, ReiThera’s gorilla-derived vector is phylogenetically and biologically distinct from vectors, such as the group E chimpanzee-derived ChAdOx1, and the group D human-derived Ad26, implicated in reported cases. “That makes it unlikely to trigger the same mechanism—but we don’t rely on assumptions,” Raggioli explained.
With this in mind, his team has initiated studies to determine whether their vector triggers pathways involved in somatic hypermutation.
“If we find any signal, we can engineer around it,” he said. “The key point is that not all adenoviruses behave the same.”
Key takeaways on adenovirus-associated thrombosis:
- Thrombosis risk appears to be both species- and vector-specific
- Gorilla-derived Group C vectors differ mechanistically and genetically from groups in which thrombotic events have been observed
- Ongoing research aims to generate definitive data
One vector, many possibilities
What began as a vaccine vector has now evolved into a backbone that is intrinsically suited to several applications that conventional platforms have struggled to address. By focusing on modular technologies, ReiThera’s approach has the potential to lower development costs, enable cross-industry collaboration, and accelerate the movement of treatments from bench to bedside.
Ultimately, the gorilla adenovirus platform illustrates how understanding and harnessing viral biology can challenge traditional industry approaches to unlock new therapeutic possibilities.
Key takeaways:
- Natural tumor selectivity and lung tropism differentiate the gorilla adenovirus from Ad5-based platforms
- The platform supports advanced strategies, including local monoclonal antibody production and combination CAR T therapy
- Emerging data suggest adenovirus-associated thrombosis risks are not universal but must be evaluated further
This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.
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