Therapeutic cancer vaccines are gaining renewed momentum. Following positive Phase III results from Moderna and Merck with a personalised mRNA cancer vaccine, a different vaccine strategy developed in the Netherlands is moving into its next phase. Newly established biotech company Revealis Biotherapeutics will further develop the TEIPP vaccine approach, which is designed to target tumor cells that have escaped conventional immune recognition.

The TEIPP vaccine was developed by researchers at Leiden University Medical Center (LUMC) and Oncode Institute. In a first Phase I/II study in 26 patients with metastatic non-small cell lung cancer, the vaccine induced a TEIPP-specific immune response in more than 80% of evaluable patients. The findings, published in Nature Communications, provided the clinical proof-of-principle to advance the technology.

Renewed Momentum for Cancer Vaccines

Therapeutic cancer vaccines have been investigated for decades, but many earlier candidates struggled to translate an immune response into clinical benefit for patients with cancer. New insights into anti-tumor immunity, better targets, combinations with immunotherapy and the timing of treatment are changing that perspective.

On 19 August, Moderna and Merck announced positive Phase III results for their personalised mRNA cancer vaccine in combination with pembrolizumab in high-risk melanoma. Revealis Biotherapeutics uses a different technology: the TEIPP vaccine targets a specific mechanism through which tumor cells escape the immune system.

Most patients do not die from the primary tumor, but from metastasized or recurrent tumors. Recent developments show that cancer vaccines can work: you can and need to teach the immune system to target cancer, sustain that immune response with checkpoint blockade, and intervene at the right moment. Our vaccine is fundamentally different from the Moderna and Merck approach, but it builds on the same underlying insight. This creates a new therapeutic opportunity.

Sjoerd van der Burg, Professor at Leiden University Medical Center; Oncode Accelerator Workstream Lead Therapeutic Vaccines

Targeting the Tumor Cells that Become Invisible

One of the major challenges in immunotherapy is that tumor cells can adapt. Some tumor cells alter their antigen presentation and as a result become almost invisible to the T cells that should attack them. These tumor cells eventually drive renewed tumor growth, while current immunotherapies may no longer work effectively. The technology behind Revealis Biotherapeutics is designed to target these escaped tumor cells and restore immune control.

Scientists led by Sjoerd van der Burg and Thorbald van Hall discovered that these “invisible” tumor cells simultaneously display specific TEIPP antigens. These arise precisely when the normal mechanism by which tumor cells present tumor antigens is disrupted.

The immune system does not naturally mount a strong response against TEIPP antigens. The vaccine teaches the immune system to recognize these TEIPP antigens and aims to turn a tumor escape mechanism into a vulnerability.

The first clinical study showed that this principle also works in patients: more than 80% developed a TEIPP-specific immune response following vaccination.

From scientific insight to company

Revealis Biotherapeutics will develop a next generation of the vaccine containing multiple TEIPP peptides. This is intended to generate a broader immune response and make the technology suitable for a larger group of patients.

For this first development phase, pre-seed financing has been brought together by Oncode BV and two family offices. Revealis Biotherapeutics will require additional capital and collaboration partners for further clinical development.

We now have not only a strong scientific concept, but also clinical proof-of-concept. Revealis Biotherapeutics brings together the expertise, financing and development strategy needed to take these results to the next stage towards an actual cancer vaccine.

Emil Pot, Business Developer at Oncode Institute

Reducing Early Risk to Enable Further Development

Oncode Institute supported the development of the original scientific concept and funded its early clinical translation through its Clinical Proof-of-Concept programme (CPoC). This allowed the researchers not only to test whether the vaccine was safe and induced the intended immune response in patients, but also to respond to new scientific insights during the study.

Following the clinical proof-of-concept, Oncode Institute also supported further valorization, from assessment of intellectual property and development strategy, to company formation and the first financing phase.

To make the vaccine as broadly applicable and robust as possible, it needs to contain multiple TEIPP antigens. The so-called “dark proteome” is an important source of tumor-specific antigens that may be used for this purpose. By drawing on the expertise and infrastructure within Oncode Accelerator, and through a Demonstrator Project, additional TEIPPs can be identified and validated for use in the TEIPP vaccine.

With the creation of Revealis Biotherapeutics, there is now a structure through which this knowledge can be developed further, attract new capital and ultimately create both economic and health value.

Cheryl Zimberlin, Managing Partner at Ligase BioPartners

Science as a Basis for Economic Impact

Revealis Biotherapeutics also illustrates the broader role of Dutch cancer science. New medicines rarely emerge in a single step. Between a scientific discovery and a treatment for patients lie years of clinical development, specialist expertise and significant investment.

By stimulating and funding curiosity-driven research, building innovative preclinical infrastructure, and helping promising discoveries to be validated and valorized, Oncode Institute and Oncode Accelerator help ensure that knowledge developed in the Netherlands can grow into new medicines, companies, intellectual property and investment.

About Revealis Biotherapeutics – revealing immune escape, restoring control

Revealis Biotherapeutics is a Dutch biotech company developing therapeutic cancer vaccines targeting TEIPP antigens. The technology is based on research from [LUMC] and targets tumor cells that have evaded conventional immune recognition due to changes in their antigen presentation. More information is available on the website: https://revealisbio.com/.

About Oncode Institute

Oncode Institute is a Dutch cancer research and innovation organisation that brings together 62 leading researchers and their teams across 13 partner institutes. By combining excellent science, collaboration and valorisation, Oncode Institute helps translate cancer research into new diagnostics, treatments and economic and societal impact. Its mission is: outsmarting cancer, impacting lives.

Website: https://www.oncodeinstitute.nl

About Ligase Biopartners 

Ligase BioPartners is a science-first life-sciences investor that creates and invests in companies translating early scientific discoveries into new therapies and diagnostics. In addition to capital, Ligase supports researchers and founders with company formation and early-stage development.