Platform

A NOVEL PERSPECTIVE ON HOW HLA GENES INFLUENCE IMMUNE RESPONSES TO CANCER

Cancers are made up of a variety of cells, each presenting a wide range of protein fragments (epitopes) on their surface. The HLA genes, which vary significantly between individuals (practically each person has a different combination of 6 HLA class I alleles), control which and how many epitopes are displayed. They also influence the effectiveness of the immune system’s response to these targets, resulting in considerable variability in how different people’s immune systems interact with their cancers. Despite advances in understanding, predicting the immune system’s response to these HLA-restricted epitopes remains challenging, leading to uncertainty in selecting new immunotherapy targets.

To explore this further, TREOS scientists studied the relationship between the immune responses of clinical trial participants and their full HLA genotype (meta-analysis on 42 cancer vaccine clinical trials). Their findings revealed that a person’s complete HLA genotype, rather than individual HLA alleles, is a key factor in determining immune responses (Lorincz et al., Cells, 2021).. Specifically, they identified, using their proprietary PEPI Test, “personal epitopes” (PEPIs), which are peptides that bind to multiple HLA alleles of a person. These PEPIs serve as genetic biomarkers, for the first time accurately predicting individual’s T cell responses (Hubbard et al CCR 2022).

Additionally, TREOS data showed that T cell responses elicited by PEPIs are stronger than thos elicited by other “common” epitopes derived from the same tumor antigen in the vaccinated patients (Hubbard et al., ESMO2024).

TREOS proposes that PEPIs could serve as key targets for designing effective immunotherapies, as they help the immune system to efficiently recognize cancer cells (abundantly presented targets) and elicit strong and broad immune responses (polyclonal T cell responses), potentially breaking the tolerance. The PEPIs may also be useful in predicting which patients will respond to our peptide-based cancer vaccines, enabling more personalized treatments using PEPI as biomarker.

DIGITAL IMMUNOTHERAPY DEVELOPMENT

PEPIs not only help predict immune responses in patients but also play a key role in determining the success of clinical trials for our PolyPEPI cancer vaccines. They drive the unprecedented immune reactions and clinical outcomes seen in our studies (Hubbard et al., ESMO2024). As a result, PEPIs are a central focus of our vaccine design platform and are incorporated into our product pipeline.

At TREOS, we use a knowledgebase and the PASCal (Personal Antigen Selection Calculator) tool to create peptide-based cancer vaccines for various solid tumors. This knowledgebase connects HLA genetics to the expression of shared tumor antigens in thousands of real-world patients, allowing us to account for the diversity in tumors and patient genetics (Lorincz et al SITC 2021).

PASCal helps us develop POLYPEPI off-the-shelf immunotherapies incorporating multiple PEPIs, that are effective for a wide range of people, regardless of their genetic background. This technology enables us to create cancer vaccines that do not require pre-screening for specific HLA alleles, making them accessible to a broader patient population.

Our proprietary PEPI biomarker allows TREOS to apply these off-the-shelf products to personalized cancer treatments. With just a simple saliva or blood sample—no tumor biopsy needed—we can tailor treatments to individual patients (PEPI PANEL products).

Our motto:

FASTER, BETTER, CHEAPER personalized immunotherapies.