Platform

PLATFORM TECHNOLOGY

Each cancer consists of a diverse mix of cells. Each person’s immune system generates an individualized response against each specific cancer cell type. This results in extreme variabilities of interactions between people’s immune systems and their cancers. To understand the mechanism behind the immunotherapeutic effect of cancer immunotherapies TREOS scientists investigated the relationship between clinical outcome and complete HLA genotype in treated individuals that participated in clinical trials. They demonstrated that an individual’s HLA class I and class II genotype is the main determinant of clinical response. Specifically, personal epitopes (PEPIs) identified with the PEPI Test are genetic biomarkers that predict peptide-specific T cell responses of individual patients with precision (Hubbard et al CCR 2022).

TREOS’s findings provided a solution to the long standing puzzle of the variability of individual patient’s clinical responses to cancer immunotherapies. The PEPI biomarker not only predicts the clinical outcome of peptide recipients but also the clinical trial outcome of cancer immunotherapies in a model population of HLA genotyped individuals (digital-twins).

IN SILICO HUMAN MODEL

TREOS’s in silico human model estimates the clinical trial outcome of cancer vaccines. At TREOS we validated the in silico human model on 2,338 subjects participating in 94 vaccine clinical trials (Lorincz et al Cells 2021). We developed this model to minimize the risk and expedite the clinical development of our peptide cancer immunotherapies.

DIGITAL IMMUNOTHERAPY DEVELOPMENT

At TREOS we use knowledgebase and algorithm embedded in PASCal (Personal Antigen Selection Calculator) tool to develop peptide cancer immunotherapies.

We created a knowledgebase by building a comprehensive taxonomy of immunological information linking HLA genetics to expression of shared tumor antigens to capture the heterogeneity of tumors by location and by time (Lorincz et al SITC 2021).

Our Peptide Target Knowledgebase currently contains 10^8 true HLA-epitope pairs derived from 1,300 tumor antigens derived from >96,000 tumor specimen across 19 different tumor types and HLA class I and class II molecules covering the HLA genotype of 26,000 subjects.

PASCAL’s algorithm selects from the knowledgebase peptides matching with the patient’s HLA alleles and tumor type. PASCal supports the development of off-the-shelf immunotherapies for single individuals (PEPI PANEL products) (Csiszovszki et al SITC 2019) and a population of individuals with a specific genetic background, including specific peptides most effective in ethnic populations (POLYPEPI products) (Hubbard et al CCR 2022).

TREOS’s proprietary PEPI biomarker enables the development of novel predictive diagnostic tests that uniquely provide the opportunity to apply TREOS’s off-the-shelf products in the personalized treatment of cancer patients, using a simple saliva sample, without the need for tumor biopsy.

Our motto:
FASTER, BETTER, CHEAPER personalized immunotherapies.