Revealis enters cancer vaccine race with TEIPP strategy
Dutch startup Revealis Biotherapeutics has launched to develop a new generation of cancer vaccines targeting tumor cells that have become difficult for T cells to recognize, building on an academic program that has already reached patients.
Why it matters: The company is going after a mechanism of resistance to cancer immunotherapy rather than the conventional tumor antigens targeted by many therapeutic vaccines. The approach could potentially complement checkpoint inhibitors and other T-cell therapies by attacking cancer cells that have escaped their initial immune pressure.
How it works: Tumors can evade T cells by disrupting their antigen-processing machinery, including by reducing the activity of TAP proteins that help display tumor antigens on the cell surface.
- Researchers at Leiden University Medical Center and Oncode Institute found that cells with impaired antigen processing display an alternative set of antigens known as TEIPPs: T-cell epitopes associated with impaired peptide processing. Revealis aims to train T cells to recognize those otherwise poorly immunogenic targets.
The backstory: Researchers tested the concept in a first-in-human Phase 1/2 study involving 26 patients with metastatic non-small cell lung cancer whose disease had progressed after checkpoint inhibitor treatment. The prototype vaccine, TEIPP24, contained a synthetic peptide derived from LRPAP1 and was restricted to patients carrying HLA-A*0201. More than 80% of evaluable patients developed TEIPP-specific immune responses following vaccination.
Yes, but: Immune activation has not yet translated into convincing efficacy data. Among 24 radiologically evaluable patients, one had a partial response, eight achieved stable disease and two showed mixed responses. Median progression-free survival was 2.1 months, and 25 of the 26 enrolled patients eventually progressed during follow-up. The trial was designed primarily to assess safety, tolerability and immunogenicity rather than efficacy.
What’s next: Revealis plans to move beyond the single-antigen prototype by developing a vaccine incorporating several TEIPP peptides. Oncode Accelerator, a public-private Dutch consortium launched in 2023 to speed up and de-risk preclinical cancer drug development, is supporting the search for additional targets, including antigens originating from the so-called dark proteome. A broader antigen set could both strengthen the immune response and reduce the patient restrictions of the first vaccine.
What we’re watching: The company has secured undisclosed pre-seed financing from Oncode BV, the venture arm of the Oncode Institute, and two family offices. At the time of publishing, the company did not respond to a request from European Biotechnology to clarify the amount raised or the identity of the investors. Revealis explained in an announcement that it will need additional financing and partners to move the program through further clinical development.
The big picture: Revealis is emerging as therapeutic cancer vaccines regain attention following recent late-stage progress for Moderna and MSD’s personalized neoantigen vaccine. While Moderna and MSD build individualized vaccines against mutations found in each patient’s tumor, Revealis wants to exploit a shared vulnerability created when tumors alter their antigen-presentation machinery. If the strategy works, immune escape itself could become the target of treatment.
